A Study of Ipatasertib in Combination with Atezolizumab and Paclitaxel as a Treatment for Patients with Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer
- Conditions
- Metastatic triple-negative breast cancer (TNBC)MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000810-12-DK
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1155
- Women or men, age >= 18 years
- Willingness and ability to complete all study-related assessments, including PRO assessments, in the investigator’s judgment
- Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1
- Life expectancy of at least 6 months
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 28 days after the final dose of ipat/placebo, 5 months after the final dose of atezo /placebo, and 6 months after the final dose of pac, whichever occurs later
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm, with female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 28 days after the final dose of ipat /placebo, or 6 months after the final dose of pac, whichever occurs later
- For any patients enrolled in the extended enrollment phase: patient is a current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry
Disease-Specific Inclusion Criteria
- Appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown or non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1 status is positive
- Histologically documented triple-negative adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
- Submittal of a formalin-fixed, paraffin-embedded tumor tissue block or a minimum of 15 freshly cut unstained, serial tumor slides from the most recently collected tumor tissue. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable
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 900
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 255
- 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
- Severe infection within 4 weeks prior to study treatment or treatment with antibiotics within 2 weeks prior to study treatment. Patients receiving prophylactic antibiotics are eligible
- Known HIV infection and clinically significant history of liver disease consistent with Child-Pugh Class B or C
- Current treatment with anti-viral therapy for hepatitis B
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle1 or anticipation of need for a major surgical procedure during the study
- 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 through Fridericia's formula > 480 ms
- Current treatment with medications used at doses known to cause clinically relevant prolongation of QT/QTc interval
- History or presence of a clinically significant abnormal Electrocardiogram
- Requirement for chronic corticosteroid therapy of > 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
Disease-Specific Exclusion Criteria
- History of or known presence of brain or spinal cord metastases during screening or prior radiographic assessments
- Known CNS disease
- Known germline BRCA1/2 deleterious mutation, unless the patient is not an appropriate candidate for a PARP-inhibitor
- Any previous systemic therapy for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast
- Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
- Patients who have received palliative radiotherapy to peripheral sites 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
- Uncontrolled pleural effusion, pericardial effusion, or ascites, tumor-related pain 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
Pac-Specific Exclusion Criteria
- Known hypersensitivity or contraindication to any component of the study treatments
- Grade >= 2 peripheral neuropathy
Ipat-Specific Exclusion Criteria
- History of Type I or Type II diabetes mellitus requiring insulin or active inflammatory bowel disease or active bowel inflammation
- Grade >= 2 un
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 the experimental arm treatment compared with control arm treatment in each cohort based on investigator-assessed progression-free survival (PFS) and overall survival (OS);Secondary Objective: • To evaluate the safety of the experimental arm treatment in each cohort<br>;Primary end point(s): 1. Investigator-assessed PFS according to RECIST v1.1 in experimental arm treatment compared with control arm treatment in each cohort (i.e., Arm A vs. Arm C and Arm B vs. Arm C in Cohort 1 and Arm A vs. Arm B in Cohort 2)<br>2. OS in experimental arm treatment compared with control arm treatment in each cohort (i.e., Arm A vs. Arm C and Arm B vs. Arm C in Cohort 1 and Arm A vs. Arm B in Cohort 2)<br>;Timepoint(s) of evaluation of this end point: 1-2. Approximately 3 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Incidence and severity of adverse events, with severity determined by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0<br>2. Change from baseline in targeted vital signs<br>3. Change from baseline in targeted clinical laboratory test results<br>;Timepoint(s) of evaluation of this end point: 1. Up to approximately 3 years<br>2-3. From baseline to SDDV<br>