A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

CO40016

This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.

2018-01-06

2023-01-04

2023-01-04

Completed

Early phase I

579

Inclusion Criteria: * Women or men aged =\>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Adequate hematologic and organ function within 14 days prior to treatment initiation * Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy) * HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy and meets one of the following: patient has recurrent disease \<=5 years of being on adjuvant endocrine therapy or if patient with de novo metastatic disease have progressed within 6 months of being on first line endocrine therapy. * Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis * Confirmation of biomarker eligibility using an appropriately validated molecular assay at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or equivalently accredited i.e., valid results from either central testing or local testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm Exclusion Criteria: * Treatment with approved or investigational cancer therapy within 14 days prior to treatment initiation * Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval) * History of or known presence of brain or spinal cord metastases * Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer) * Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed) * History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills * Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents) * Known human immunodeficiency virus (HIV) infection * Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of treatment (or anticipated need during study) * Pregnant or breastfeeding, or intending to become pregnant during the study * Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction \[LVEF\] \<50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram \[ECG\] abnormalities). * Need for chronic corticosteroid therapy of \>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease * Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy * Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy) * History of Type I or Type II diabetes mellitus requiring insulin * Grade \>=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia * History of or active inflammatory bowel disease or active bowel inflammation * Clinically significant lung disease (including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of opportunistic infections) * Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of treatment * Grade \>=2 peripheral neuropathy

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 579, 'type': 'ACTUAL'}}

2024-03-12