Back to resultsA Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer (IPATunity150)
Primary Purpose
Breast Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ipatasertib
Placebo
Palbociclib
Fulvestrant
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
- Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
- At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
- Phase III only: Tumor specimen from the most recently collected, available tumor tissue
Exclusion Criteria:
- Pregnant or breastfeeding, or intending to become pregnant
- Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
- Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
- Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
- Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
- History of Type I or Type II diabetes mellitus requiring insulin
- History of or active inflammatory bowel disease or active bowel inflammation
- Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections
Sites / Locations
- Piedmont Cancer Institute, PC
- University of Chicago Medical Center
- Massachusetts General Hospital
- Dana-Farber Cancer Institute; GYN Oncology
- Summit Medical Group; MD Anderson Cancer Center
- Cabrini Medical Centre; Oncology
- Sunshine Hospital
- Hospital das Clinicas - UFRGS
- Hospital Sao Lucas - PUCRS
- Tom Baker Cancer Centre-Calgary
- Juravinski Cancer Clinic; Clinical Trials Department
- Hopital du Saint Sacrement
- National Hospital Organization Kyushu Cancer Center
- Kanagawa Cancer Center
- Asan Medical Center
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona
- Hospital Clínico Universitario de Valencia; Servicio de Oncología
- The Royal Marsden Hospital; Dept of Medicine
- Christie Hospital NHS Trust
- Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
Phase 3: Placebo + Palbociclib + Fulvestrant
Arm Description
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) in Intent-to-Treat (ITT), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Progression-Free Survival (PFS) in Patients with PIK3CA/AKT1/PTEN Altered Tumors, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Secondary Outcome Measures
Objective Response Rate (ORR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Duration of Objective Response (DOR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Clinical Benefit Rate (CBR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Overall Survival (OS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1
Time to Deterioration (TTD) in Severity of Pain, according to the Brief Pain Inventory-Short Form (BPI-SF)
TTD in presence and interference of pain according to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale
Time to deterioration (TTD) in physical functioning (PF)
TTD in Role Functioning (RF)
TTD in Global Health Status (GHS)/Quality of Life (QoL)
Number of Participants with Adverse Events
Phase 1b: Plasma Concentration of Ipatasertib and its Metabolite, G-037720 and Palbociclib
Phase 3: Plasma Concentration of Ipatasertib or its Placebo and its Metabolite, G-037720
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04060862
Brief Title
A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Acronym
IPATunity150
Official Title
A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 15, 2019 (Actual)
Primary Completion Date
August 29, 2023 (Actual)
Study Completion Date
August 29, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant
Arm Type
Experimental
Arm Title
Phase 3: Placebo + Palbociclib + Fulvestrant
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Other Intervention Name(s)
RO5532961, GDC-0068
Intervention Description
Phase 1b: Ipatasertib, 300 mg starting dose administered orally once daily (PO QD) during an initial 5-7 day run-in period, then continued on Days 1-21 during the first cycle. Starting with Cycle 2, Day 1 ipatasertib will be taken orally once daily on Days 1-21 of each 28-day cycle. Phase 3: Ipatasertib, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Phase 3: Matching placebo, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Intervention Description
Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
Fulvestrant, 500 mg administered as two intramuscular injections of 250 mg each on Cycle 1 Days 1 and 15 and Day 1 of each subsequent 28-day cycle.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) in Intent-to-Treat (ITT), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Title
Progression-Free Survival (PFS) in Patients with PIK3CA/AKT1/PTEN Altered Tumors, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Title
Duration of Objective Response (DOR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Title
Clinical Benefit Rate (CBR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Title
Overall Survival (OS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1
Time Frame
From randomization in Phase 3 until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 64 months
Title
Time to Deterioration (TTD) in Severity of Pain, according to the Brief Pain Inventory-Short Form (BPI-SF)
Time Frame
From randomization in Phase 3 to the first documentation of a 2-point or more increase in pain scale from baseline, up to approximately 64 months
Title
TTD in presence and interference of pain according to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale
Time Frame
From randomization in Phase 3 to the first documentation of a 10-point or more increase from baseline, up to approx 64 months
Title
Time to deterioration (TTD) in physical functioning (PF)
Time Frame
From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the PF scale of the EORTC QLQ-C30, up to approx 64 months
Title
TTD in Role Functioning (RF)
Time Frame
From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the RF scale of the EORTC QLQ-C30, up to approx 64 months
Title
TTD in Global Health Status (GHS)/Quality of Life (QoL)
Time Frame
From randomization in Phase 3 to the first documentation of a 10-point or more decrease from baseline in the GHS/HRQoL scale of the EORTC QLQ-C30, up to approx 64 months
Title
Number of Participants with Adverse Events
Time Frame
From baseline to end of study, up to approximately 64 months
Title
Phase 1b: Plasma Concentration of Ipatasertib and its Metabolite, G-037720 and Palbociclib
Time Frame
Ipatasertib & G-037720: predose, postdose at 0.5,1,2,3,4,6hr of Cycle(C) 1 (each cycle is 28 days), Day(D) 1, postdose at 0.5,1,2,3,4,6hr of C1D15, 2hr post-dose on C3D15; Palbociclib: predose on C1D15, C2D15 & C3D15
Title
Phase 3: Plasma Concentration of Ipatasertib or its Placebo and its Metabolite, G-037720
Time Frame
2-4 hrs after ipatasertib or its placebo on C1D1 (each cycle is 28 days), C1D15 and C2D15, Predose on C1D15, C2D15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
Phase III only: Tumor specimen from the most recently collected, available tumor tissue
Exclusion Criteria:
Pregnant or breastfeeding, or intending to become pregnant
Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
History of Type I or Type II diabetes mellitus requiring insulin
History of or active inflammatory bowel disease or active bowel inflammation
Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections
Facility Information:
Facility Name
Piedmont Cancer Institute, PC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114-2621
Country
United States
Facility Name
Dana-Farber Cancer Institute; GYN Oncology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Summit Medical Group; MD Anderson Cancer Center
City
Florham Park
State/Province
New Jersey
ZIP/Postal Code
07932
Country
United States
Facility Name
Cabrini Medical Centre; Oncology
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
Sunshine Hospital
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Hospital das Clinicas - UFRGS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Hospital Sao Lucas - PUCRS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Tom Baker Cancer Centre-Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Juravinski Cancer Clinic; Clinical Trials Department
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Hopital du Saint Sacrement
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1S 4L8
Country
Canada
Facility Name
National Hospital Organization Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia; Servicio de Oncología
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
The Royal Marsden Hospital; Dept of Medicine
City
London
ZIP/Postal Code
SW3 5PT
Country
United Kingdom
Facility Name
Christie Hospital NHS Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study 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).
Learn more about this trial
A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
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