A Study to Compare Atezolizumab (Anti-PD-L1 Antibody) in Combinationwith Adjuvant Anthracycline/Taxane based Chemotherapy VersusChemotherapy Alone in Patients with Operable Triple-Negative BreastCancer
- Conditions
- Triple-negative breast cancer (TNBC)MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003695-47-DE
- 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
- All
- Target Recruitment
- 1986
- 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 breastconserving
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
- 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
- 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/epirubicin, 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, , or doxorubicin/epirubicin or 12 months after the last dose of cyclophosphamide whichever is later
- Women who are not postmenopausal and 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
F.1.2.1 Number of subjects for this age range 1574
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 412
- Prior history of invasive breast cancer
- Any T4 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 and/or cerebrovascular 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
- Positive HIV test at screening
- Active hepatitis B, C virus infection and tuberculosis
- 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 the course of the study
- 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