a study of ipatasertib in combination with paclitaxel as a treatment for participants with pik3ca/akt1/pten-altered, locally advanced or metastatic, triple-negative breast cancer or hormone receptor-positive, her2-negative breast cancer

Conditions: Breast Cancer

Summary: 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.


Eligibility criteria:
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