A Randomized, Double-Blind, Phase III Clinical Trial of Neoadjuvant Chemotherapy with Atezolizumab or Placebo in Patients with Triple-Negative Breast Cancer Followed by Adjuvant Continuation of Atezolizumab or Placebo GeparDouze

Phase 1

• Conditions: Patients with early breast cancer; MedDRA version: 20.0Level: LLTClassification code: 10007050Term: Cancer Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508472-11-00
• Lead Sponsor: SABP Foundation Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-02
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1550

Inclusion Criteria

The patient must have consented to participate and, prior to beginning specific study procedures, must have signed and dated an appropriate IRBapproved consent form that conforms to federal and institutional guidelines for study treatment and for submission of tumor samples as required by NSABP B-59/GBG 96-GeparDouze for baseline correlative science studies., Ipsilateral axillary lymph nodes must be evaluated by imaging (ultrasound, and/or MRI) within 42 days prior to study entry. If suspicious or abnormal, FNA or core biopsy is recommended. Findings of these evaluations will be used to define the nodal status prior to study entry according to the following criteria: Nodal status – negative - Imaging of the axilla is negative; - Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative; Nodal status – positive - FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive. - Imaging is suspicious or abnormal but FNA or core biopsy was not performed., Patients with synchronous bilateral or multicentric HER2-negative breast cancer are eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets stage eligibility criteria. All of the other invasive tumors must also be HER2-negative by ASCO/CAP Guidelines based on local testing. Central testing to confirm TNBC status is only required for the highest risk tumor., Blood counts performed within 28 days prior to randomization must meet the following criteria: • ANC must be = 1500/mm3; • platelet count must be = 100,000/mm3; and • hemoglobin must be = 10 g/dL., The following criteria for evidence of adequate hepatic function performed within 28 days prior to randomization must be met: • total bilirubin must be = ULN for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin; and • alkaline phosphatase must be = 2.5 x ULN for the lab; and • AST and ALT must be = 1.5 x ULN for the lab., Patients with AST or ALT or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, abdominal ultrasound, PET-CT, or PET scan) performed within 28 days prior to randomization does not demonstrate metastatic disease and the requirements in criterion 13 are met., Patients with alkaline phosphatase that is > ULN but = 2.5 x ULN or with unexplained bone pain are eligible for inclusion in the study if bone imaging (bone scan, PET-CT scan, or PET scan) supported by additional studies when indicated (CT, x-ray, MRI) performed within 42 days prior to randomization does not demonstrate metastatic disease., Patients with N2 or N3 nodal disease or T3 primary disease must undergo liver imaging within 28 days prior to randomization and bone imaging (as described in criteria 14 and 15) within 42 days prior to randomization, irrespective of baseline lab results, and studies must not demonstrate metastatic disease. Chest imaging with chest x-ray PA and Lateral, CT of the chest, or PET-CT must also be performed., Creatinine clearance = 50 mL/min (see Section 7.2.1 for instructions regarding calculation of creatinine clearance) performed within 28 days prior to randomization., PT/INR = ULN within 28 days prior to randomization. For laboratories that do not report an ULN for the INR assay, use = 1.2 as the value for the ULN. Patients receiving therapeutic anti-coagulants are not eligible.,

Exclusion Criteria

Excisional biopsy or lumpectomy performed prior to study entry., Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to: Active cardiac disease: - angina pectoris that requires the use of anti-anginal medication; - ventricular arrhythmias except for benign premature ventricular contractions; - supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; - conduction abnormality requiring a pacemaker; - valvular disease with documented compromise in cardiac function; or - symptomatic pericarditis. History of cardiac disease: - myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function within 6 months prior to randomization; - history of documented CHF; or - documented cardiomyopathy., Uncontrolled hypertension defined as sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg. (Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.) Patients requiring = 3 BP medications are not eligible., History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins., Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells., Known allergy or hypersensitivity to the components of the atezolizumab formulation., Known allergy or hypersensitivity to the components of the doxorubicin, epirubicin, cyclophosphamide, carboplatin, or paclitaxel formulations., Known allergy or hypersensitivity to liposomal or pegylated G-CSF formulations., Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix B) with the following exceptions: - Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. - Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. - Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted provided all of following conditions are met: • Rash must cover < 10% of body surface area. • Disease is well controlled at baseline and requires only lowpotency topical corticosteroids. • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months., History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan., Positive test for HIV., FNA alone to diagnose the breast cancer., Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negativ

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified