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-ES
- Lead Sponsor
- Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1150
- 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; if tumor status is known to be PD-L1+, the patient should be an appropriate candidate for atezolizumab + paclitaxel)
- 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 897
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 640
-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 systemic anti-microbial treatment-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 virus
-Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to D1 of C1 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 D1 of C1
-Congenital long QT syndrome or screening QT interval corrected through use 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 an abnormal Electrocardiogram that is clinically significant in the investigator's opinion
-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 14days prior to D1 of C1
-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, as determined by computed tomography (CT) or magnetic resonance imaging evaluation 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 D1 of C1 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 D1 of C1, 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 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
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