A placebo-controlled study of Ipatasertib in combination with Atezolizumab and Paclitaxel as a treatment for patients with advanced breast cancer

Phase 3

Recruiting

• Conditions: Malignant neoplasm of breast

• Registration Number: RBR-2x8xh8
• Lead Sponsor: Hospital Perola Byington

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-25
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: Not specified

Inclusion Criteria

Women or men with 18 to 65 years with locally advanced unresectable or metastatic triple-negative adenocarcinoma of the breast who have not received prior systemic chemotherapy in this setting may be eligible for this study. In patients with BRCA-associated tumors, platinum chemotherapy as potentially the preferred treatment option should be taken into consideration when determining whether this study may be appropriate for these patients. Patients may have received prior chemotherapy in the neoadjuvant or adjuvant setting if treatment was completed at least 12 months prior to randomization. Locally advanced unresectable disease must not be amenable to resection with curative intent. Patients must have sufficient tumor tissue and comply with all eligibility criteria to be enrolled. Signature (s) of Free and Informed Consent (s) signed; Women or men, aged 18 or over at the moment of signing the Informed Consent Term; Provision and ability to conduct all assessments related to the study, including PRO assessments, in the investigator's judgment; Measurable disease according to RECIST (Pre-irradiated lesions may be considered as measurable disease only if the progressive disease has been unequivocally documented at that location since the radiation.); Functional Capacity of 0 or 1 according to the Collaboration Group in East-American Oncology; Adequate hematological and organ function within 14 days before the first treatment of the study on Day 1 of Cycle 1; Life expectancy of at least 6 months; For women of childbearing potential: agree to remain abstinent or use contraception and agree to refrain from donating eggs; For men agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agree to refrain from donating sperm, a histologically documented triple-negative breast adenocarcinoma that is locally advanced or metastatic and is not amenable to resection with curative intent; Dispatch of a formalin-fixed and paraffin-embedded tumor tissue block (FFPE) or at least 15 freshly cut serial tumor blades not stained from the most recently collected tumor tissue (for PD-L1 status and other secondary and exploratory assessments required by the Protocol). Cytology or FNA samples will not be acceptable. Tumor tissue of bone metastases that is submitted to decalcification will not be acceptable; If a more recent sample is insufficient or unavailable, a patient may still be eligible if the patient can provide a block of tissue (preferred) or at least 15 unblotted serial slides of an older tumor archived tissue or is willing to consent and undergo an extra thick or excisional needle biopsy of the non-target lesion on pre-treatment (if it is accessible and the biopsy can be safely obtained). In general, at least three biopsies per thick needle will be required;

Exclusion Criteria

Inability to adhere to study and follow-up procedures; History of malabsorption syndrome or other condition that would interfere with enteral absorption or result in inability or unwillingness to swallow pills; Active infection requiring systemic antimicrobial treatment (including antibiotics, antifungal agents and antiviral agents); Known HIV infection (there should be a negative HIV test at screening); A clinically significant history of liver disease consistent with Child-Pugh B or C Class including active viral hepatitis or other hepatitis, current drug / drug or alcohol or cirrhosis abuse; Current treatment with antiviral therapy for HBV; Large surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Cycle 1 Day 1 or anticipated need for a large surgical procedure during the study; Placement of a vascular access device will not be considered a major surgery; Pregnancy or lactation or intention to become pregnant during the study or within 28 days after the final dose of ipatasertibe / placebo, 5 months after the final dose of atezolizumab / placebo and 6 months after the final dose of paclitaxel, whichever occurs later; Class II, III or IV heart failure according to the New York Heart Association, ejection fraction left ventricle less than 50% or active ventricular arrhythmia requiring medication; Unstable angina present or history of myocardial infarction within 6 months before Day 1 of Cycle 1; Congenital long QT syndrome or QT interval corrected by the Fridericia formula (QTcF) at screening more than 480 ms; History or presence of an abnormal ECG that is clinically significant in the investigator's opinion (including complete left bundle branch block, second or third degree heart block or evidence of prior myocardial infarction); Need for chronic corticosteroid therapy more than 10 mg prednisone per day or equivalent dose of other anti-inflammatory corticosteroids or immunosuppressive agents for a chronic disease; Any other disease, metabolic dysfunction, physical examination findings, or clinical laboratory findings that in the investigator's opinion lead to reasonable suspicion of a disease or condition that contravenes the use of a investigational drug or that may affect the interpretation of the results or puts the patient at high risk for treatment complications; History of or known presence of brain or spinal metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or previous radiographic evaluations; Any previous systemic therapy for locally advanced or metastatic triple inoperable breast adenocarcinoma; Patients who have received palliative radiotherapy for peripheral sites;Pleural effusion, pericardial effusion or uncontrolled ascites; Known hypersensitivity or contraindication to any component of the study treatments, including the excipient of paclitaxel, macrogolglycerol ricinoleate; Peripheral neuropathy Grade greater than or equal to 2; History of Type I or Type II diabetes mellitus requiring insulin; History of or autoimmune disease or active immunodeficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain- Barré or multiple sclerosis

Study & Design

• Study Type: Intervention
• Study Design: Not specified