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

Breast Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04060862
• Other study ID #: CO41012
• Secondary ID: 2019-001072-11
• Status: Terminated
• Phase: Phase 3
• Start date: November 15, 2019
• Est. completion date: August 29, 2023

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: August 29, 2023
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Ipatasertib
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.
• Placebo
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.
• Palbociclib
Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.
• Fulvestrant
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.

Locations

Country	Name	City	State
Australia	Cabrini Medical Centre; Oncology	Malvern	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Canada	Tom Baker Cancer Centre-Calgary	Calgary	Alberta
Canada	Juravinski Cancer Clinic; Clinical Trials Department	Hamilton	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Kanagawa Cancer Center	Kanagawa
Korea, Republic of	Asan Medical Center	Seoul
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
United Kingdom	The Royal Marsden Hospital; Dept of Medicine	London
United Kingdom	Christie Hospital NHS Trust	Manchester
United Kingdom	Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit	Sutton
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	Dana-Farber Cancer Institute; GYN Oncology	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Summit Medical Group; MD Anderson Cancer Center	Florham Park	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		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
Primary	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)		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	Objective Response Rate (ORR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)		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	Duration of Objective Response (DOR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)		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	Clinical Benefit Rate (CBR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)		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	Overall Survival (OS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1		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	Time to Deterioration (TTD) in Severity of Pain, according to the Brief Pain Inventory-Short Form (BPI-SF)		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
Secondary	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		From randomization in Phase 3 to the first documentation of a 10-point or more increase from baseline, up to approx 64 months
Secondary	Time to deterioration (TTD) in physical functioning (PF)		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
Secondary	TTD in Role Functioning (RF)		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
Secondary	TTD in Global Health Status (GHS)/Quality of Life (QoL)		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
Secondary	Number of Participants with Adverse Events		From baseline to end of study, up to approximately 64 months
Secondary	Phase 1b: Plasma Concentration of Ipatasertib and its Metabolite, G-037720 and Palbociclib		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
Secondary	Phase 3: Plasma Concentration of Ipatasertib or its Placebo and its Metabolite, G-037720		2-4 hrs after ipatasertib or its placebo on C1D1 (each cycle is 28 days), C1D15 and C2D15, Predose on C1D15, C2D15