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
- Conditions
- Hormone receptor (HR)-positive/HER2-negative locally advanced unresectable or metastatic breast cancerMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001072-11-ES
- Lead Sponsor
- Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 370
- Age >= 18 years
- 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 a condom, 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170
- 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 Ib only: Prior treatment with CDK4/6 inhibitor
- 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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in the intent to treat (ITT) population and in patients with PIK3CA/AKT1/PTEN altered tumors (Phase III);Secondary Objective: 1. To evaluate additional efficacy of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in the ITT population and in patients with PIK3CA/AKT1/PTEN altered tumors (Phase III)<br>2. To characterize the safety of combining ipatasertib with palbociclib + fulvestrant (Phase Ib and III)<br>3. To characterize the Pharmacokinetic profiles of ipatasertib and its metabolite (G-037720) in combination with palbociclib and fulvestrant (Phase Ib and III);Primary end point(s): 1. Progression-free survival (PFS) in ITT patients<br>2. PFS in patients with PIK3CA/AKT1/PTEN altered Tumors;Timepoint(s) of evaluation of this end point: Phase III<br>1-2. Up to 64 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Phase III<br>1. Objective response rate (ORR)<br>2. Duration of objective response (DOR)<br>3. Clinical benefit rate (CBR)<br>4. Overall survival (OS)<br>5. Time to deterioration (TTD) in pain<br>6. TTD in physical functioning, role functioning, and Global Health Survey/Health-Related Quality of Life<br><br>Phase Ib and III<br>7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0<br>8. Change from baseline in targeted vital signs<br>9. Change from baseline in targeted clinical laboratory test results<br>10. Plasma concentration of ipatasertib and its metabolite, G-037720, at specified timepoints;Timepoint(s) of evaluation of this end point: 1-9. Up to 64 months<br>10. Phase Ib: Cycle 1 Day 1 and 15; Cycle 2 and 3 Day 15; Phase III: Cycle 1 Day 1 and 15; Cycle 2 Day 15