A Study to Compare Atezolizumab (Anti-PD-L1 Antibody) in Combination with Adjuvant Anthracycline/Taxane based Chemotherapy Versus Chemotherapy Alone in Patients with Operable Triple-Negative Breast Cancer
- Conditions
- Triple-negative breast cancer (TNBC)MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003695-47-GB
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 2300
- Age >= 18 years
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Non-metastatic operable Stage II-III breast cancer; patients with node-negative disease must have a pathologic tumor size > 2cm
- Histologically documented TNBC that is centrally confirmed
- Confirmed tumor Programmed death-ligand 1 (PD-L1) evaluation (centrally conducted)
- Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
- Pathological tumor-node-metastasis staging: Patient must have had sentinel lymph node biopsy and/or axillary lymph node dissection for evaluation of pathologic nodal status
- Patients with synchronous bilateral invasive disease are eligible only if all bilateral invasive lesions are histologically confirmed as triple negative by central lab and have completed adequate pathological tumor-node metastasis staging bilaterally as described
- No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization
- Baseline left ventricular ejection fraction >= 53% measured by echocardiogram or multiple-gated acquisition scans
- Adequate hematologic and end-organ function
- Negative HIV test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV)
DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
- Representative formalin-fixed, paraffin embedded tumor specimen from surgical resection in paraffin blocks or at least 25 unstained slides, with an associated pathology report documenting locally assessed ER, PgR, and HER2 negativity
Patients with 20 to 25 unstained slides available at baseline may be eligible upon discussion with the Medical Monitor.
- For women of childbearing potential: agreement to remain abstinent or use contraceptive measures that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, or 6 months after the last dose of paclitaxel or doxorubicin, or 12 months after the last dose of cyclophosphamide. Women must refrain from donating eggs during the same period.
- For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and 6 months after the last dose of paclitaxel, cyclophosphamide, or doxorubicin/epirubicin
- Women who are not postmenopausal or have not undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
- Prior history of invasive breast cancer
- Any T4 clinical tumor
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment planned in the context of this study
- Previous therapy with anthracyclines or taxanes for any malignancy
- History of ductal carcinoma in situ and/or lobular carcinoma in situ that was treated with any form of systemic, hormonal therapy, or radiotherapy (RT) to the ipsilateral breast where invasive cancer subsequently developed
- Contraindication to RT when adjuvant RT is clinically indicated
- Cardiopulmonary dysfunction
- Prior malignancies within 5 years prior to randomization
- 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 any component of the atezolizumab, paclitaxel, cyclophosphamide, or doxorubicin/epirubicin formulations and filgrastim or pegfilgrastim or granulocyte-macrophage colony-stimulating factor formulations
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- Current treatment with anti-viral therapy for HBV
- Urinary outflow obstruction
- Severe infections within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment
- Prior allogeneic stem cell or solid organ transplant
- Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or within 5 months after the last dose of atezolizumab
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Prior treatment with CD137 agonists or immune checkpoint-blockade therapies
- Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
- Pregnant or lactating, or intending to become pregnant during the study
- Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease
- Under any legal protection (tutorship/curatorship)
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