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A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors (LOTUS)

Primary Purpose

Breast Neoplasms

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ipatasertib
Paclitaxel
Placebo
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasms

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen, required prior to randomization
  • Measurable disease, according to the RECIST v1.1
  • Adequate hematologic and organ function within 14 days before the first study treatment
  • For female participants of childbearing potential, agreement (by both participant and partner) to use an effective form of contraception for the duration of the study and for 6 months after last dose of study treatment

Exclusion Criteria:

  • Any previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>/=) 6 months prior to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with curative intent
  • Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
  • Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer
  • Previous therapy with Akt, PI3K, and/or mTOR inhibitors
  • Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Known presence of the brain or spinal cord metastasis, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments

Sites / Locations

  • St Jude Heritage Medical Group
  • Cedars Sinai Medical Center
  • Cancer Care Assoc Med Group
  • UCLA Medical Center
  • Holycross Medical Group
  • Memorial Healthcare System
  • Hematology Oncology Associates of the Treasure Coast
  • Rush University Medical Center
  • Cancer Center of Kansas
  • Massachusetts General Hospital Cancer Center
  • Comprehensive Cancer Centers of Nevada
  • Carolinas Healthcare System
  • The WEST CLINIC, P.C.
  • MD Anderson Cancer Center
  • Northern Utah Associates
  • Northwest Medical Specialties
  • West Virginia University Hospitals Inc
  • Sint Augustinus Wilrijk
  • Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
  • Centre Francois Baclesse
  • Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
  • Hopital Saint Louis; Oncologie Medicale
  • Clinique Armoricaine de Radiol
  • Istituto Nazionale Tumori Fondazione G. Pascale
  • Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
  • Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera
  • National Cancer Center
  • Seoul National University Bundang Hospital
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University Health System
  • Asan Medical Center
  • Korea University Guro Hospital
  • National University Hospital; National University Cancer Institute, Singapore (NCIS)
  • National Cancer Centre
  • Hospital Universitari Vall d'Hebron
  • Institut Catala d Oncologia Hospital Duran i Reynals
  • Complejo Hospitalario de Jaen
  • MD Anderson Cancer Center
  • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Farmacia
  • Hospital Virgen del Rocio
  • China Medical University Hospital
  • Chi Mei Medical Center, Yong kang; Endocrinology
  • National Taiwan University Hospital
  • Chang Gung Medical Foundation - Linkou; Dept of Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ipatasertib + Paclitaxel

Placebo + Paclitaxel

Arm Description

Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.

Secondary Outcome Measures

PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause.
OS in Participants With PTEN-Low Tumors
OS was defined as the time from the date of randomization to the date of death from any cause.
OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors
OS was defined as the time from the date of randomization to the date of death from any cause.
Objective Response Rate (ORR)
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
ORR in Participants With PTEN-Low Tumors
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Confirmed tumor ORR in subjects with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of subjects who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Subjects for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Duration of Response
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Duration of Response in Participants With PTEN-Low Tumors
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Duration of objective response in participants with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time to Disease Progression
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time to Disease Progression in Participants With PTEN-Low Tumors
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Safety: Percentage of Participants With Adverse Events
An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib
PK parameters were not calculated due to sparse PK sampling.
Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib
PK parameters were not calculated due to sparse PK sampling.
Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score
EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1=Not at all to 4=Very much; 2 questions used 7-point scale [1=very poor to 7=Excellent]). Scores averaged, transformed to 0-100 scale; a higher score=better level of functioning. For symptom scale scores, higher level=severe level of symptoms. "A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). PRO measures were analyzed from baseline up to cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).
PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30
Subjects reporting >/= 10-point increase compared to baseline (Cycle 1 Day 1) were considered "improved", those reporting <10-point difference were considered "remained stable", and those reporting >/=10-point decrease were considered "worsened". A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). Patient reported outcome measures were analyzed from baseline up to and including cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).

Full Information

First Posted
June 11, 2014
Last Updated
February 18, 2021
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02162719
Brief Title
A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors
Acronym
LOTUS
Official Title
A Randomized, Phase II, Multi-Center, Placebo-Controlled Study of Ipatasertib (GDC-0068), an Inhibitor of Akt, in Combination With Paclitaxel as Front-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 19, 2014 (Actual)
Primary Completion Date
June 7, 2016 (Actual)
Study Completion Date
August 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary
This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ipatasertib + Paclitaxel
Arm Type
Experimental
Arm Description
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Arm Title
Placebo + Paclitaxel
Arm Type
Placebo Comparator
Arm Description
Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Other Intervention Name(s)
GDC-0068
Intervention Description
Participants received ipatasertib orally 400 milligrams (mg) daily on Days 1-21 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Participants received paclitaxel 80 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received oral placebo matched to ipatasertib, daily on Days 1-21 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Title
PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
Description
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Secondary Outcome Measure Information:
Title
PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors
Description
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Title
Overall Survival (OS)
Description
OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
Title
OS in Participants With PTEN-Low Tumors
Description
OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
Title
OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description
OS was defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
Title
Objective Response Rate (ORR)
Description
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
ORR in Participants With PTEN-Low Tumors
Description
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description
Confirmed tumor ORR in subjects with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of subjects who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Subjects for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Duration of Response
Description
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Duration of Response in Participants With PTEN-Low Tumors
Description
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description
Duration of objective response in participants with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Time to Disease Progression
Description
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Time to Disease Progression in Participants With PTEN-Low Tumors
Description
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Description
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1.
Time Frame
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
Title
Safety: Percentage of Participants With Adverse Events
Description
An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame
Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months)
Title
Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib
Description
PK parameters were not calculated due to sparse PK sampling.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8
Title
Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib
Description
PK parameters were not calculated due to sparse PK sampling.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 8
Title
Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score
Description
EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1=Not at all to 4=Very much; 2 questions used 7-point scale [1=very poor to 7=Excellent]). Scores averaged, transformed to 0-100 scale; a higher score=better level of functioning. For symptom scale scores, higher level=severe level of symptoms. "A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). PRO measures were analyzed from baseline up to cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).
Time Frame
Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1
Title
PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30
Description
Subjects reporting >/= 10-point increase compared to baseline (Cycle 1 Day 1) were considered "improved", those reporting <10-point difference were considered "remained stable", and those reporting >/=10-point decrease were considered "worsened". A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). Patient reported outcome measures were analyzed from baseline up to and including cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).
Time Frame
Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen, required prior to randomization Measurable disease, according to the RECIST v1.1 Adequate hematologic and organ function within 14 days before the first study treatment For female participants of childbearing potential, agreement (by both participant and partner) to use an effective form of contraception for the duration of the study and for 6 months after last dose of study treatment Exclusion Criteria: Any previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>/=) 6 months prior to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with curative intent Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1 Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer Previous therapy with Akt, PI3K, and/or mTOR inhibitors Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study Known presence of the brain or spinal cord metastasis, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
St Jude Heritage Medical Group
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Cancer Care Assoc Med Group
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1772
Country
United States
Facility Name
UCLA Medical Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Holycross Medical Group
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Memorial Healthcare System
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Hematology Oncology Associates of the Treasure Coast
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3728
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89014
Country
United States
Facility Name
Carolinas Healthcare System
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28208
Country
United States
Facility Name
The WEST CLINIC, P.C.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Northern Utah Associates
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403
Country
United States
Facility Name
Northwest Medical Specialties
City
Lakewood
State/Province
Washington
ZIP/Postal Code
98499
Country
United States
Facility Name
West Virginia University Hospitals Inc
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26056
Country
United States
Facility Name
Sint Augustinus Wilrijk
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
Hopital Saint Louis; Oncologie Medicale
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Clinique Armoricaine de Radiol
City
Saint Brieuc
ZIP/Postal Code
22015
Country
France
Facility Name
Istituto Nazionale Tumori Fondazione G. Pascale
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
National Cancer Center
City
Goyang-si
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
ZIP/Postal Code
13605
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
ZIP/Postal Code
08308
Country
Korea, Republic of
Facility Name
National University Hospital; National University Cancer Institute, Singapore (NCIS)
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
National Cancer Centre
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Institut Catala d Oncologia Hospital Duran i Reynals
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Complejo Hospitalario de Jaen
City
Jaen
ZIP/Postal Code
23007
Country
Spain
Facility Name
MD Anderson Cancer Center
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Farmacia
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
China Medical University Hospital
City
North Dist.
ZIP/Postal Code
40402
Country
Taiwan
Facility Name
Chi Mei Medical Center, Yong kang; Endocrinology
City
Tainan
ZIP/Postal Code
710
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Chang Gung Medical Foundation - Linkou; Dept of Surgery
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Citations:
PubMed Identifier
28800861
Citation
Kim SB, Dent R, Im SA, Espie M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1360-1372. doi: 10.1016/S1470-2045(17)30450-3. Epub 2017 Aug 8. Erratum In: Lancet Oncol. 2018 Dec;19(12):e667.
Results Reference
derived

Learn more about this trial

A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors

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