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 (IPATunity150)

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ipatasertib; Drug: Palbociclib; Drug: Fulvestrant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Cabrini Medical Centre; Oncology
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre-Calgary
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Clinic; Clinical Trials Department
  • Quebec
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint Sacrement
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia; Servicio de Oncología
• United Kingdom
  • London, United Kingdom, SW3 5PT
    • The Royal Marsden Hospital; Dept of Medicine
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute, PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2621
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute; GYN Oncology
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group; MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant	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.; Other Names: RO5532961, GDC-0068; Drug: Palbociclib; Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.; Drug: 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.
Placebo Comparator: Phase 3: Placebo + Palbociclib + Fulvestrant	Drug: Palbociclib; Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.; Drug: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
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
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
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
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
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
Number of Participants with Adverse Events	From baseline to end of study, up to approximately 64 months
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Actual): August 29, 2023
• Study Completion (Actual): August 29, 2023

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant; Palbociclib; Ipatasertib
• Other Study ID Numbers: CO41012; 2019-001072-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No