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

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

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.

Trial Description

Primary Outcome:

• Progression-Free Survival (PFS) in Intent-to-Treat (ITT), as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST v1.1)
• Progression-Free Survival (PFS) in Patients with PIK3CA/AKT1/PTEN Altered Tumours, as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST v1.1)

• Objective Response Rate (ORR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST v1.1)
• Duration of Objective Response (DOR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST v1.1)
• Clinical Benefit Rate (CBR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST v1.1)
• Overall Survival (OS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumours, 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

View this trial on ClinicalTrials.gov