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A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

Primary Purpose

Neoplasms, Breast Neoplasms

Status

Active

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

talazoparib

About this trial

This is an interventional treatment trial for Neoplasms focused on measuring Phase 1, talazoparib, PF-06944076, MDV3800, BMN673, PARP inhibitor, Japanese, solid tumors, breast cancer, C3441030

Eligibility Criteria

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

[Dose Escalation Part]

Inclusion Criteria:

Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
ECOG Performance Status 0 or 1.
Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

Patients with known symptomatic brain metastases requiring steroids.
Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment.
Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

[Dose Expansion Part]

Inclusion Criteria:

Histologically or cytologically confirmed carcinoma of the breast.
Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease.
Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test.
No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease.
Have measurable lesion by the RECIST v.1.1.
ECOG Performance Status 0-2.
Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

First-line locally advanced or metastatic breast cancer with no prior neoadjuvant and adjuvant chemotherapy.
Prior treatment with a PARP inhibitor.
Objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease.
HER2 positive breast cancer.
Active inflammatory breast cancer.
Central nervous system (CNS) metastases.
Current or anticipated use within 7 days prior to the first dose of study treatment, or anticipated use during the study of strong P-gp inhibitors.
Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

talazoparib

Arm Description

0.75 mg/day or 1.0 mg/day

Outcomes

Primary Outcome Measures

Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)

DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (>)7days; Febrile neutropenia >1 hour; G greater than or equal to (>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for >=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)>5*upper limit of normal(ULN) and 2*increases above baseline values; ALT/AST>=3*ULN concurrent with total bilirubin (TB)>2*ULN; TB>5*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib.

Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.

Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator.

Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported.

Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry

Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.

Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology

Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.

Dose Escalation: Number of Participants With Abnormalities in Vital Signs

Vital sign abnormalities: a) Sitting systolic blood pressure: <90 millimeter of mercury (mmHg), decrease from baseline >=30 mmHg, increase from baseline >=30 mmHg; b) Sitting diastolic blood pressure: minimum <50 mmHg, decrease from baseline >=20 mmHg, increase from baseline >=20 mmHg; c) Sitting pulse rate: minimum <40 beats per minute (bpm), maximum >120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure.

Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib

Cmax was defined as the maximum observed plasma concentration of talazoparib.

Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib

Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib

Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib

Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F)

Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib

Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).

Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib

Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.

Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib

Pre dose plasma concentration of talazoparib.

Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib

Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).

Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib

Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours.

Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss)

Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib

Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours.

Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib

Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Dose Escalation: Progression Free Survival (PFS)

PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.

Dose Escalation: Duration of Response (DOR)

DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.

Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.

Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12

OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported.

Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib

Pre dose plasma drug concentration.

Full Information

NCT ID

NCT03343054

First Posted

November 11, 2017

Last Updated

September 19, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT03343054

Brief Title

A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

Official Title

A PHASE 1 STUDY OF THE SAFETY, PHARMACOKINETICS AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB, POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR, IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 30, 2017 (Actual)

Primary Completion Date

January 11, 2021 (Actual)

Study Completion Date

August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part. The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available. In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs. The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations. In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.

6. Conditions and Keywords

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

Neoplasms, Breast Neoplasms

Keywords

Phase 1, talazoparib, PF-06944076, MDV3800, BMN673, PARP inhibitor, Japanese, solid tumors, breast cancer, C3441030

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

talazoparib

Arm Type

Experimental

Arm Description

0.75 mg/day or 1.0 mg/day

Intervention Type

Drug

Intervention Name(s)

talazoparib

Intervention Description

Talazoparib will be administered orally on a continuous basis. Talazoparib may be taken with or without food. Each cycle will consist of 28 days.

Primary Outcome Measure Information:

Title

Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)

Description

Time Frame

Cycle 1 (28 days)

Title

Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

Description

Time Frame

From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

Description

Time Frame

From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)

Title

Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

Description

Time Frame

Title

Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

Description

Time Frame

Title

Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry

Description

Time Frame

Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days

Title

Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology

Description

Time Frame

Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days

Title

Dose Escalation: Number of Participants With Abnormalities in Vital Signs

Description

Time Frame

Baseline up to 286 days

Title

Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib

Description

Cmax was defined as the maximum observed plasma concentration of talazoparib.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib

Description

Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib

Description

Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib

Description

Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F)

Description

Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib

Description

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib

Description

Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib

Description

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1

Title

Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib

Description

Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib

Description

Pre dose plasma concentration of talazoparib.

Time Frame

Pre dose on Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib

Description

Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib

Description

Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss)

Description

Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib

Description

Time Frame

Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1

Title

Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib

Description

Time Frame

Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1

Title

Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Description

Time Frame

From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)

Title

Dose Escalation: Progression Free Survival (PFS)

Description

Time Frame

From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days)

Title

Dose Escalation: Duration of Response (DOR)

Description

Time Frame

From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)

Title

Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Description

Time Frame

From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Title

Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Description

Time Frame

Baseline up to Week 16, Baseline up to Week 24

Title

Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Description

Time Frame

Baseline up to Week 16, Baseline up to Week 24

Title

Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Description

Time Frame

From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)

Title

Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Description

Time Frame

From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)

Title

Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Description

Time Frame

From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Title

Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Description

Time Frame

From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Title

Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

Description

Time Frame

From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)

Title

Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)

Description

Time Frame

From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)

Title

Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12

Description

Time Frame

At Month 12

Title

Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib

Description

Pre dose plasma drug concentration.

Time Frame

Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

[Dose Escalation Part] Inclusion Criteria: Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available. ECOG Performance Status 0 or 1. Adequate Bone Marrow, Renal and Liver Function. Exclusion Criteria: Patients with known symptomatic brain metastases requiring steroids. Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment. Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception. [Dose Expansion Part] Inclusion Criteria: Histologically or cytologically confirmed carcinoma of the breast. Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease. Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test. No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease. Have measurable lesion by the RECIST v.1.1. ECOG Performance Status 0-2. Adequate Bone Marrow, Renal and Liver Function. Exclusion Criteria: First-line locally advanced or metastatic breast cancer with no prior neoadjuvant and adjuvant chemotherapy. Prior treatment with a PARP inhibitor. Objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease. HER2 positive breast cancer. Active inflammatory breast cancer. Central nervous system (CNS) metastases. Current or anticipated use within 7 days prior to the first dose of study treatment, or anticipated use during the study of strong P-gp inhibitors. Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Aichi Cancer Center Hospital

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

464-8681

Country

Japan

Facility Name

National Cancer Center Hospital East

City

Kashiwa

State/Province

Chiba

ZIP/Postal Code

277-8577

Country

Japan

Facility Name

National Hospital Organization Hokkaido Cancer Center

City

Sapporo

State/Province

Hokkaido

ZIP/Postal Code

003-0804

Country

Japan

Facility Name

Kanagawa Cancer Center

City

Yokohama

State/Province

Kanagawa

ZIP/Postal Code

241-8515

Country

Japan

Facility Name

Saitama Cancer Center

City

Kitaadachi-gun

State/Province

Saitama

ZIP/Postal Code

362-0806

Country

Japan

Facility Name

National Cancer Center Hospital

City

Chuo-Ku

State/Province

Tokyo

ZIP/Postal Code

104-0045

Country

Japan

Facility Name

Hakuaikai Medical Corporation Sagara Hospital

City

Kagoshima

ZIP/Postal Code

892-0833

Country

Japan

Facility Name

National Hospital Organization Osaka National Hospital

City

Osaka

ZIP/Postal Code

540-0006

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Citations:

PubMed Identifier

35907135

Citation

Kotani H, Masuda N, Yamashita T, Naito Y, Taira T, Inoue K, Takahashi M, Yonemori K, Toyoizumi S, Mori Y, Nagasawa T, Hori N, Iwata H. Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30.

Results Reference

derived

PubMed Identifier

34160752

Citation

Naito Y, Kuboki Y, Ikeda M, Harano K, Matsubara N, Toyoizumi S, Mori Y, Hori N, Nagasawa T, Kogawa T. Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study. Invest New Drugs. 2021 Dec;39(6):1568-1576. doi: 10.1007/s10637-021-01120-7. Epub 2021 Jun 23.

Results Reference

derived

Links:

URL

https://pmiform.com/clinical-trial-info-request?StudyID=C3441030

Description

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Learn more about this trial

A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

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A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

Neoplasms, Breast Neoplasms

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial