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Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer

Primary Purpose

Early Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

TALAZOPARIB

About this trial

This is an interventional treatment trial for Early Breast Cancer focused on measuring Neoadjuvant Therapy, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE Breast Cancer, BRCA Positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Germline BRCA 1/2 Mutation Positive
Women and men at least 18 years of age or older.
Histologically confirmed invasive adenocarcinoma of the breast
HER2 negative breast cancer as defined by ASCO-CAP criteria
Tumor greater than or equal toT1, N0-3
No evidence of distant metastasis
Adequate bone marrow, hepatic, and renal function
ECOG performance status 0 or 1

Exclusion Criteria:

Any other previous antitumor therapies for the current cancer event. Treatment for ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and radiation.
Evidence of distant metastasis apparent prior to randomization
Patients with inflammatory breast carcinoma
Malignancy within the last 3 years, except: Stage 1 melanoma which does not require any further treatment after adequate surgical excision; adequately treated non melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade 1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which has been disease free for a year; Other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for 5 years.
Previous or concomitant systemic anti cancer therapies used for the treatment of cancer in the last 3 years.
Prior treatment with a PARP inhibitor in any disease setting
Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors
Patients who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol
Major surgery within 14 days prior to study entry
Known history of cardiac disease, for example : Myocardial infarction or symptomatic cardiac ischemia within 24 weeks before screening; Congestive heart failure New York Heart Association Class III or IV; History of clinically significant ventricular arrhythmias within one year prior to randomization; History of Mobitz II second degree or third degree heart block, uncontrolled hypertension.
Active clinically significant infection
Clinically significant bleeding diathesis or coagulopathy
Non healing wound, ulcer or bone fracture
Known hypersensitivity to any of the components of talazoparib
Patients with myelodysplastic syndrome/acute myeloid leukemia
Patients with uncontrolled seizures.
Any evidence of other disease or any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment

Sites / Locations

Banner Gateway Medical Center
Banner MD Anderson Cancer Center
Highlands Oncology Group
Highlands Oncology Group
PMK Medical Group Inc., dba Ventura County Hematology Oncology Specialists
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
City of Hope Investigational Drug Services (IDS)
The Oncology Institute of Hope & Innovation
Glendale Adventist Medical Center
The Oncology Institute of Hope & Innovation
UC Irvine Health
UC Irvine Medical Center
PMK Medical Group Inc., dba Ventura County Hematology Oncology Specialists
Emad Ibrahim, MD, INC.
The Oncology Institute of Hope & Innovation
Stanford Cancer Institute
Stanford Hospital and Clinics
Stanford Women's Cancer Center
PMK Medical Group Inc., dba Ventura County Hematology Oncology Specialists
The Oncology Institute of Hope & Innovation
The Oncology Institute of Hope & Innovation
ICRI
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Innovative Medical Research of South Florida, Inc
Grady Health System
Emory University Hospital Midtown
Emory University Hospital
The Emory Clinic
Winship Cancer Institute
Emory Saint Joseph's Hospital
Rush University Medical Center, Professional Office Building Infusion Pharmacy
Rush University Medical Center
Rush Oak Park Hospital
University of Mississippi Medical Center
Summit Medical Group
Summit Medical Group PA
St. Luke's Hospital - Warren Campus
St. Luke's Warren Physician Group
Northwest Cancer Specialists, P.C.
Northwest Cancer Specialists, P.C.
Northwest Cancer Specialists, P.C.
St. Luke's Hematology Oncology Specialists
St. Luke's Hospital - Allentown Campus
St. Luke's Hematology Oncology Specialists
St. Luke's Hospital - Bethlehem Campus
St. Luke's Hospital - Miners Campus
St Luke's Hospital - Anderson Campus
St. Luke's Hospital - Anderson Campus
UPMC Hillman Cancer Center Mountainview Arnold Palmer Pavilion
UPMC Cancer Centers East Oxford Drive
Magee-Womens Hospital of UPMC
UPMC Hillman Cancer Center
UPMC Hillman Cancer Center North Hills at Passavant
UPMC Hillman Cancer Center UPMC Passavant
St. Luke's Hospital - Quakertown Campus
St. Luke's Hospital - Monroe Campus
UPMC Hillman Cancer Center Uniontown
UPMC Hillman Cancer Center Washington
Charleston Hematology Oncology Associates, PA
Avera Cancer Institute
Avera Specialty Hospital
Brig Center for Cancer Care and Survivorship
Baptist Cancer Center
Texas Oncology - Allen
Texas Oncology - Austin Midtown
Texas Oncology-Austin Central
Texas Oncology - South Austin
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Texas Oncology-Denton South
The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center
U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376
U.T. MD Anderson Cancer Center
US Oncology Investigational Products Center (IPC)
Texas Oncology - McKinney
Texas Oncology - Round Rock
Virginia Oncology Associates
Virginia Oncology Associates
Virginia Oncology Associates
Virginia Oncology Associates
Virginia Oncology Associates
Northwest Cancer Specialists, P.C.
Northwest Cancer Specialists, P.C.
University of Wisconsin Clinical Science Center
UW Health University Hospital - Pharmaceutical Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TALAZOPARIB

Arm Description

SINGLE ARM, NON-RANDOMIZED

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Pathological Complete Response (pCR) as Per Independent Central Review (ICR) in Evaluable Analysis Set as Per ICR With 80% Confidence Interval (CI)

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current American Joint Committee on Cancer [AJCC] staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR as Per ICR in Evaluable Analysis Set as Per ICR With 95% CI

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Secondary Outcome Measures

Percentage of Participants Achieving pCR as Per ICR in Intention-to-Treat (ITT) Analysis Set With 80% CI

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR as Per ICR in ITT Analysis Set With 95% CI

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR as Per Investigator in Evaluable Analysis Set as Per Investigator

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per Investigator). The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR as Per Investigator in ITT Analysis Set

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR in Breast Only as Per Investigator in Evaluable Analysis Set as Per Investigator

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by investigator was defined as the percentage of participants achieving pCR in breast by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per Investigator). The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR in Breast Only as Per Investigator in ITT Analysis Set

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR in Breast Only as Per ICR in Evaluable Analysis Set as Per ICR

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR in Breast Only as Per ICR in ITT Analysis Set

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Percentage of Participants With Residual Cander Burden (RCB) as Per ICR in Evaluable Analysis Set as Per ICR

The RCB is a continuous index derived from the following: primary tumor dimensions; cellularity of the tumor bed; axillary nodal burden. Residual cancer burden by ICR is reported as a categorical variable with four classes (categories): RCB 0 (pCR), I (minimal RCB), II (moderate RCB), III (extensive RCB). Participants who had progressive disease or was unable to be assessed for RCB due to missing required axillary specimen were counted in the "Missing" category. The simultaneous exact CI was calculated using Goodman's method.

Percentage of Participants With RCB as Per ICR in ITT Analysis Set

Probability of Being Event-Free at 3 Years in Evaluable Analysis Set

Event-Free Survival (EFS) is defined as the time from surgery date to first documentation of local or distant recurrence or death or initiation of antineoplastic therapy before documentation of first relapse. Participants discontinuing study before documentation of first relapse or death, but after surgery were censored observations for EFS. EFS at 3 years is defined as the probability of being event free at 3 years after surgery using Kaplan Meier methods.

Probability of Being Alive at 3 Years in Evaluable Analysis Set

Overall Survival (OS) is defined as the time from first dose of talazoparib to death due to any cause. Participants not known to have died at the time of the analysis were right censored on the date they were last known to be alive before the analysis data cutoff date. OS at 3 years is defined as the probability of being alive at 3 years after first dose of talazoparib using Kaplan Meier methods.

Probability of Being Alive at 3 Years in ITT Analysis Set

OS is defined as the time from first dose of talazoparib to death due to any cause. Participants not known to have died at the time of the analysis were right censored on the date they were last known to be alive before the analysis data cutoff date. OS at 3 years is defined as the probability of being alive at 3 years after first dose of talazoparib using Kaplan Meier methods.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or worsened relative to pretreatment state. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE.

Number of Participants With Serious Adverse Events (SAEs)

An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.

Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Drug

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.

Number of Participants With TEAEs Leading to Temporary Discontinuation of Study Drug

Number of Participants With TEAEs Leading to Dose Reduction of Study Drug

Number of Participants With Laboratory Abnormalities

Laboratory parameters included hematology, serum chemistry, urinalysis and coagulation. Grades of laboratory abnormalities were defined according to NCI CTCAE version 4.03. Participants with laboratory test abnormalities meeting specified criteria (>upper limit of normal [ULN] or <lower limit of normal [LLN]) (without regards to baseline abnormality) are reported.

Number of Participants With Hematology Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Hematology laboratory parameters included hematocrit, hemoglobin, mean corpuscular volume, red blood cells, platelets, white blood cells with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils). Grades of lab results were defined by NCI CTCAE version 4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE. This outcome measure was based only on laboratory data. As Grade 4 anemia cannot be assessed based only on laboratory data, it was not applicable for analysis in this outcome measure.

Number of Participants With Chemistry Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Chemistry laboratory parameters included albumin, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, non-fasting glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and lactate dehydrogenase. Grades of laboratory results were defined by NCI CTCAE version 4.03. Grade 1 (Mild) = asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 (Moderate ) = minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3 = severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4 = events with life-threatening consequences, urgent intervention indicated; Grade 5 = death related to AE.

Trough Plasma Concentration (Ctrough) of Talazoparib in Cycles 2, 3 and 4 in PK Analysis Set

Within-Participant Average Ctrough of Talazoparib at Steady State in PK Analysis Set

Within-participant average Ctrough of talazoparib at steady state for each participant was defined as the average (mean) value of the steady state Ctrough values (Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1 trough concentrations) for each individual participant.

Ctrough of Talazoparib in Cycles 2, 3 and 4 in Dose-Compliant PK Analysis Set

Within-Participant Average Ctrough of Talazoparib at Steady State in Dose-Compliant PK Analysis Set

Number of Participants Who Achieved Definitive Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Per European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire (EORTC QLQ-30)

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes (PROs), consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease.

Kaplan-Meier Estimate of Time to Definitive Deterioration in GHS/QoL Per EORTC QLQ-30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease.

Probability of Not Achieving Definitive Deterioration in GHS/QoL Per EORTC QLQ-C30 at 3 and 6 Months

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all to 4=very much). For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease. Probability of not achieving definitive deterioration (being event-free) at specified time points (3 and 6 months post-baseline) using the Kaplan Meier method were reported.

Number of Participants Who Achieved Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.

Kaplan-Meier Estimate of Time to Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.

Probability of Not Achieving Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 at 3 and 6 Months

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, with 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores (1=very poor to 7=excellent); other items have 4 possible scores (1=not at all to 4=very much). For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A linear transformation was applied to raw scores so that transformed scores lie between 0 to 100, with 0 being the best and 100 being the worst for this symptom scale. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as≥10 point increase from baseline without any subsequent <10 point increase. Probability of not achieving definitive deterioration (being event-free) at specified time points (3 and 6 months post-baseline) using Kaplan Meier method were reported.

Change From Baseline in Global QoL Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. Negative change from baseline indicates deterioration in GHS/QoL and positive change indicates improvement.

Change From Baseline in Physical Functioning Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the physical functioning scale, participants self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. Negative change from baseline indicates deterioration in physical functioning and positive change indicates improvement.

Change From Baseline in Role Functioning Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the role functioning scale, participants self-rated how much they were limited in doing work or daily activities, or in pursuing hobbies or other leisure time activities during the past week. Negative change from baseline values indicates deterioration in role functioning and positive change indicates improvement.

Change From Baseline in Emotional Functioning Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the emotional functioning scale, participants self-rated how much they felt tense, worried, irritable or depressed during the past week. Negative change from baseline values indicates deterioration in emotional functioning and positive change indicates improvement.

Change From Baseline in Cognitive Functioning Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the cognitive functioning scale, participants self-rated the extent of difficulty in concentrating on things or remembering things during the past week. Negative change from baseline values indicates deterioration in cognitive functioning and positive change indicates improvement.

Change From Baseline in Social Functioning Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the social functioning scale, participants self-rated how much their physical condition or medical treatment interfered with their family life and social activities during the past week. Negative change from baseline values indicates deterioration in social functioning and positive change indicates improvement.

Change From Baseline in Fatigue Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the fatigue symptoms scale, participants self-rated how much they had felt weak, tired or needed to rest during the past week. Negative change from baseline values indicates improvement of fatigue symptoms and positive change indicates deterioration.

Change From Baseline in Nausea and Vomiting Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. Negative change from baseline values indicates improvement of nausea and vomiting symptoms and positive change indicates deterioration.

Change From Baseline in Pain Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the pain symptoms scale, participants self-rated the extent of pain and how much the pain interfered with daily activities during the past week. Negative change from baseline values indicates improvement of pain symptoms and positive change indicates deterioration.

Change From Baseline in Dyspnoea Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the dyspnoea symptoms scale, participants self-rated the intensity of shortness of breath during the past week. Negative change from baseline values indicates improvement of dyspnoea symptoms and positive change indicates deterioration.

Change From Baseline in Insomnia Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the insomnia symptoms scale, participants self-rated the intensity of shortness of breath during the past week. Negative change from baseline values indicates improvement of insomnia symptoms and positive change indicates deterioration.

Change From Baseline in Appetite Loss Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the appetite loss symptoms scale, participants self-rated the extent of lack of appetite during the past week. Negative change from baseline values indicates improvement of appetite loss symptoms and positive change indicates deterioration.

Change From Baseline in Constipation Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the constipation symptoms scale, participants self-rated the intensity of constipation during the past week. Negative change from baseline values indicates improvement of constipation symptoms and positive change indicates deterioration.

Change From Baseline in Diarrhea Symptoms Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the diarrhea symptoms scale, participants self-rated the intensity of diarrhea during the past week. Negative change from baseline values indicates improvement of diarrhea symptoms and positive change indicates deterioration.

Change From Baseline in Financial Difficulties Per EORTC QLQ-C30

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the symptom scale of financial difficulties, participants self-rated how much their physical condition or medical treatment caused financial difficulties. Negative change from baseline values indicates improvement of financial difficulties and positive change indicates deterioration.

Change From Baseline in Body Image Per EORTC QLQ Breast Cancer Quality of Life Questionnaire (EORTC QLQ-BR23)

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the functional scale of body image, participants self-rated how much they felt physically less attractive or less feminine, difficult to look at themselves naked, or dissatisfied with their body during the past week. Negative change from baseline indicates worsening of self-rated body image and positive change indicates improvement.

Change From Baseline in Sexual Functioning Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the sexual functioning scale, participants self-rated to what extent they were interested in sex and were sexually active (with or without intercourse) during the past 4 weeks. Negative change from baseline values indicates worsening of sexual functioning and positive change indicates improvement.

Change From Baseline in Sexual Enjoyment Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the functional scale of sexual enjoyment, participants self-rated to what extent sex was enjoyable for them during the past 4 weeks. Negative change from baseline values indicates worsening of sexual enjoyment and positive change indicates improvement.

Change From Baseline in Future Perspective Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the functional scale of future perspective, participants self-rated how much they were worried about their health in the future. Negative change from baseline values indicates worsening of future perspective and positive change indicates improvement.

Change From Baseline in Systemic Therapy Side Effects Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the systemic therapy side effects scale, participants self-rated the intensity of symptoms of dry mouth, unusual taste, pain and irritation of eyes, hair loss, feeling ill or unwell, hot flushes and headaches during the past week. Negative change from baseline= improvement of these side effects, positive change = deterioration.

Change From Baseline in Breast Symptoms Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the breast symptoms scale, participants self-rated how much they had pain or skin problems (e.g. itchy, dry, flaky) on or in the area of affected breast, and how much this area was swollen or oversensitive during the past week. Negative change from baseline indicates improvement of breast symptoms and positive change indicates deterioration.

Change From Baseline in Arm Symptoms Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the arm symptoms scale, participants self-rated how much they had pain in the arm or shoulder, how much the arm or hand was swollen, and difficulty in raising the arm or moving it sideways. Negative change from baseline indicates improvement of arm symptoms and positive change indicates deterioration.

Change From Baseline in Upset by Hair Loss Per EORTC QLQ-BR23

EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the upset by hair loss scale, participants self-rated how upset they were due to loss of hair during the past week. Negative change from baseline values indicates improvement of upset by hair loss and positive change indicates deterioration.

Number of Participants With Deterioration in Nausea/Vomiting Symptoms

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Deterioration in nausea and vomiting symptoms was defined as a 10 point or more increase from baseline for that specific time point.

Number of Participants With Improvement in Nausea/Vomiting Symptoms

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Improvement in nausea and vomiting symptoms was defined as a 10 point or more decrease from baseline for that specific time point.

Number of Participants With No Change in Nausea/Vomiting Symptoms

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all to 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. No change in nausea/vomiting symptoms=having neither deterioration (≥10 point increase from baseline) nor improvement (≥10 point decrease from baseline) for the time point.

Number of Participants With Missed Expected Menstrual Periods Per Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Missed expected menstrual period was assessed electronically using the PRO CTCAE questionnaire, a PRO measure developed to evaluate symptomatic toxicity in patients on cancer clinical trials. This objective captures the concept of fertility preservation through PRO, since there is a possible fertility sparing effect of talazoparib versus chemotherapy.

Full Information

NCT ID

NCT03499353

First Posted

April 9, 2018

Last Updated

October 11, 2021

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT03499353

Brief Title

Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer

Official Title

A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Terminated

Why Stopped

This study was terminated based on Pfizer's change in clinical development strategy not related to safety and efficacy.

Study Start Date

August 27, 2018 (Actual)

Primary Completion Date

September 23, 2020 (Actual)

Study Completion Date

September 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Detailed Description

TALAZOPARIB (PARP INHIBITOR) FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER. THIS IS A MONOTHERAPY TREATMENT FOR 24 WKS FOLLOWED BY SURGERY TO EVALUATE PATHOLOGICAL COMPLETE RESPONSE.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Early Breast Cancer

Keywords

Neoadjuvant Therapy, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE Breast Cancer, BRCA Positive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

THIS IS AN OPEN LABEL SINGLE ARM STUDY

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TALAZOPARIB

Arm Type

Experimental

Arm Description

SINGLE ARM, NON-RANDOMIZED

Intervention Type

Drug

Intervention Name(s)

TALAZOPARIB

Intervention Description

Talazoparib 1mg/day

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving Pathological Complete Response (pCR) as Per Independent Central Review (ICR) in Evaluable Analysis Set as Per ICR With 80% Confidence Interval (CI)

Description

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR as Per ICR in Evaluable Analysis Set as Per ICR With 95% CI

Description

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving pCR as Per ICR in Intention-to-Treat (ITT) Analysis Set With 80% CI

Description

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR as Per ICR in ITT Analysis Set With 95% CI

Description

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR as Per Investigator in Evaluable Analysis Set as Per Investigator

Description

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per Investigator). The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR as Per Investigator in ITT Analysis Set

Description

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR in Breast Only as Per Investigator in Evaluable Analysis Set as Per Investigator

Description

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR in Breast Only as Per Investigator in ITT Analysis Set

Description

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR in Breast Only as Per ICR in Evaluable Analysis Set as Per ICR

Description

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants Achieving pCR in Breast Only as Per ICR in ITT Analysis Set

Description

pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants With Residual Cander Burden (RCB) as Per ICR in Evaluable Analysis Set as Per ICR

Description

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Percentage of Participants With RCB as Per ICR in ITT Analysis Set

Description

Time Frame

Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

Title

Probability of Being Event-Free at 3 Years in Evaluable Analysis Set

Description

Time Frame

3 years after surgery

Title

Probability of Being Alive at 3 Years in Evaluable Analysis Set

Description

Time Frame

3 years after first dose of talazoparib

Title

Probability of Being Alive at 3 Years in ITT Analysis Set

Description

Time Frame

3 years after first dose of talazoparib

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With Serious Adverse Events (SAEs)

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Drug

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With TEAEs Leading to Temporary Discontinuation of Study Drug

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With TEAEs Leading to Dose Reduction of Study Drug

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With Laboratory Abnormalities

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With Hematology Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Number of Participants With Chemistry Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Description

Time Frame

Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months)

Title

Trough Plasma Concentration (Ctrough) of Talazoparib in Cycles 2, 3 and 4 in PK Analysis Set

Time Frame

Pre-dose on Day 1 of Cycles 2, 3, 4

Title

Within-Participant Average Ctrough of Talazoparib at Steady State in PK Analysis Set

Description

Time Frame

Pre-dose on Day 1 of Cycles 2, 3, 4

Title

Ctrough of Talazoparib in Cycles 2, 3 and 4 in Dose-Compliant PK Analysis Set

Time Frame

Pre-dose on Day 1 of Cycles 2, 3, 4

Title

Within-Participant Average Ctrough of Talazoparib at Steady State in Dose-Compliant PK Analysis Set

Description

Time Frame

Pre-dosing on Day 1 of Cycles 2, 3, 4

Title

Description

Time Frame

Baseline to End of Treatment visit (assessed for maximum of 33 weeks)

Title

Kaplan-Meier Estimate of Time to Definitive Deterioration in GHS/QoL Per EORTC QLQ-30

Description

Time Frame

Baseline to End of Treatment visit (assessed for maximum of 33 weeks)

Title

Probability of Not Achieving Definitive Deterioration in GHS/QoL Per EORTC QLQ-C30 at 3 and 6 Months

Description

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all to 4=very much). For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease. Probability of not achieving definitive deterioration (being event-free) at specified time points (3 and 6 months post-baseline) using the Kaplan Meier method were reported.

Time Frame

3 months and 6 months post-baseline

Title

Number of Participants Who Achieved Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30

Description

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.

Time Frame

Baseline to End of Treatment visit (assessed for maximum of 33 weeks)

Title

Kaplan-Meier Estimate of Time to Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30

Description

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.

Time Frame

Baseline to End of Treatment visit (assessed for maximum of 33 weeks)

Title

Probability of Not Achieving Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 at 3 and 6 Months

Description

Time Frame

3 months and 6 months post-baseline

Title

Change From Baseline in Global QoL Per EORTC QLQ-C30

Description

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. Negative change from baseline indicates deterioration in GHS/QoL and positive change indicates improvement.

Time Frame