Description:
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.
Title
- 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
- 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 IDs
- ORG STUDY ID:
CO41012
- SECONDARY ID:
2019-001072-11
- NCT ID:
NCT04060862
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Ipatasertib | RO5532961, GDC-0068 | Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant |
| Placebo | | Phase 3: Placebo + Palbociclib + Fulvestrant |
| Palbociclib | | Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant |
| Fulvestrant | | Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant |
Purpose
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 Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant | Experimental | | - Ipatasertib
- Palbociclib
- Fulvestrant
|
| Phase 3: Placebo + Palbociclib + Fulvestrant | Placebo Comparator | | - Placebo
- Palbociclib
- Fulvestrant
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Number of Participants with Adverse Events |
| Time Frame: | From baseline to end of study, up to approximately 64 months |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
May 10, 2021
