A clinical trial of ipatasertib in combination with paclitaxel versus placebo and paclitaxel in patients with specific tumor alteration, Locally Advanced or Metastatic, Triple Negative Breast cancer or Hormone Receptor – Positive, HER2 – Negative Breast Cancer
- Conditions
- Malignant neoplasm of breast of unspecified site,
- Registration Number
- CTRI/2019/05/019047
- Lead Sponsor
- F HoffmannLa Roche Ltd
- Brief Summary
This protocolencompasses two studies, or cohorts, of different patient populations that willindependently evaluate the safety, efficacy, and pharmacokinetics of ipatasertibin combination with paclitaxel (ipatasertib + paclitaxel) compared with placeboplus paclitaxel (placebo + paclitaxel) in patients with *PIK3CA/AKT1/PTEN*-altered tumors.
One cohort will be afirst-line treatment in patients with locally advanced or metastatictriple-negative breast cancer (TNBC),
and the second will bea first-chemotherapy treatment in patients with advanced hormone receptor-positive, humanepidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who arenot appropriate candidates for endocrine therapy.
Patients will bescreened for *PIK3CA/AKT1/PTEN*-altered tumors andwill be allocated to one of the cohorts based on hormone-receptor status.HER2-positive patients are not eligible.
The reason that the twopatient populations will be evaluated separately is that TNBC and HR+/HER2- breast cancers havedifferent biologics that manifest clinically in different prognoses andresponse to treatment, and molecularly with distinctly different molecularprofiles with dissimilar oncogenic drivers. The
two populations havedifferent prevalences and progression-free survival (PFS) and overall survival(OS) expectations, and thus different enrollment and analysis timelines.
The two independenttarget patient populations for this study are premenopausal and postmenopausalfemale and male patients with measurable, locally advanced or metastatic TNBCand HR+/HER2- breast cancer who havenot received chemotherapy in either of these settings. Patients must beappropriate candidates for taxane monotherapy.
In particular, patientswith HR+/HER2- breast cancer should besuitable for treatment with chemotherapy, chemotherapy is allowed, provided ithas been concluded at least 12 months before disease recurrence.
Patients with *PIK3CA/AKT1/PTEN*-altered tumors will beassigned to Cohort A (TNBC) or Cohort B (HR+/HER2- breast cancer) based ontheir hormone receptor status (as evaluated locally, or on study, only if localevaluation is not available, with additional slides submitted for this purpose)and randomized with a 2:1 ratio to the experimental versus control arm. All primary,secondary, exploratory, and safety objectives will be assessed independentlyfor each cohort (i.e., Cohort A: patients with TNBC with *PIK3CA/AKT1/PTEN*-altered tumors andCohort
B: patients with HR+/HER2- breast cancer with *PIK3CA/AKT1/PTEN*-altered tumors).
The primary endpointfor the Cohort A (TNBC) is PFS. The primary endpoint for Cohort B (HR+/HER2- breast cancer) is alsoPFS. The primary analysis for each cohort will be independent and triggered bycohort-specific events and will also be independent of the readout of the othercohort. The secondary endpoints for each cohort will be tested if the primary analysisof the respective PFS reaches statistical significance at the level of 5%.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- All
- Target Recruitment
- 450
- Informed Consent Woman or man age 18 years and above Inoperable locally advanced/metastatic breast cancer (LA/MBC), Histologically documented TNBC or HR+/HER2– adenocarcinoma and suitable for taxane monotherapy At least 12 month disease-free interval from last chemotherapy/radiation treatment for early BC.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1 Life expectancy of at least 6 months Measurable disease according to RECIST v1.1 formalin-fixed, paraffin-embedded tumor (FFPE) tissue, [PIK3CA/AKT1/PTEN-altered status and central ctDNA] Adequate hematologic and organ function within 14 days before the first study treatment Fasting total serum glucose ≤ 150 mg/dL and HbA1C ≤ 7.5%,.
Active infection requiring systemic anti-microbial treatment, Known HIV infection, Active viral or other Hepatitis New York Heart Association Class II, III, or IV heart failure, LVEF less than 50% History of or known presence of brain or spinal cord metastases by CT/ MRI Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2– adenocarcinoma of the breast Uncontrolled pleural effusion, pericardial effusion, or ascites History of or active Inflammatory bowel disease, Lung disease Prior treatment with an AKT inhibitor (Prior PI3K or mTOR inhibitors are allowed) No uncontrolled disease/unresolved toxicity or clinically relevant condition which may contraindicate use of an investigational drug.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Investigator-assessed PFS from randomization to | the first occurrence of disease progression, as | determined locally by the investigator through | the use of RECIST v1.1, or death from any | cause, whichever occurs first
- Secondary Outcome Measures
Name Time Method OS, ORR, DoR, CBR, patient-reported pain (cohort B only) and HRQoL ORR-CR or
Trial Locations
- Locations (6)
Grant Medical Foundation Ruby Hall Clini
🇮🇳Pune, MAHARASHTRA, India
HCG cancer center
🇮🇳Ahmadabad, GUJARAT, India
Indraprashtha Apollo Hospitals
🇮🇳Delhi, DELHI, India
Max Super Specialty Hospital
🇮🇳Delhi, DELHI, India
Rajiv Gandhi Cancer Institute & Research Centre
🇮🇳West, DELHI, India
Tata Memorial Centre, Tata Memorial Hospital
🇮🇳Mumbai, MAHARASHTRA, India
Grant Medical Foundation Ruby Hall Clini🇮🇳Pune, MAHARASHTRA, IndiaDr Minish JainPrincipal investigator9823133390minishjain009@gmail.com