A 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
- Conditions
- ocally advanced or metastatic triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer or locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer with PIK3CA/AKT1/PTEN-altered tumor and no prior chemotherapy in the advanced settingMedDRA 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
- EUCTR2017-001548-36-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 450
General Inclusion Criteria
- Woman or man age =>18 years at the time of signing the Informed Consent Form
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and organ function
- Life expectancy of at least 6 months
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib/placebo and 6 months after the last dose of paclitaxel, whichever occurs later
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 28 days after the last dose of ipatasertib or 6 months after the last dose of paclitaxel, whichever occurs later
Disease-Specific Inclusion Criteria
- Locally assessed, 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
- Submission of a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or a minimum of 20 freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis. Cytologic or FNA samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable.
- Valid results from central testing confirming PIK3CA/AKT1/PTEN-altered status in tumor tissue by next-generation sequencing (NGS)
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 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90
General Exclusion Criteria:
- Inability to comply with study and follow-up procedures
- 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 antibiotics
- Known HIV infection
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the course of the study
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the last dose of ipatasertib/placebo and within 6 months after the last dose of paclitaxel, whichever occurs later
- New York Heart Association Class II, III, or IV heart failure; left ventricular ejection fraction <50%; or active ventricular arrhythmia requiring medication
- Current unstable angina or history of myocardial infarction within 6 months prior to Day 1 of Cycle 1
- Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) >480 milliseconds
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
- 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
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1
Disease-Specific Exclusion Criteria:
- History of or known presence of brain or spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments
- Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2– adenocarcinoma of the breast
- Unresolved, clinically significant toxicity from prior therapy
- For patients with HR+/HER2– breast cancer, endocrine therapy (alone or with approved targeted therapy such as CDK4/6 inhibitors or everolimus) must not be considered an appropriate option per local clinical guidelines
- Patients who have received palliative radiation treatment to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrollment)
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled tumor-related pain
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1 except for appropriately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, or Stage I uterine cancer
Ipatasertib-Specific Exclusion Criteria:
- History of Type I or Type II diabetes mellitus requiring insulin
- Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- History of or active inflamm
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method