A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination with Paclitaxel Compared with Placebo with Paclitaxel for Patients with Previously Untreated Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer
- Conditions
- Triple Negative Breast Cancer (TNBC)MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004024-29-SK
- Lead Sponsor
- F. Hoffmann-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
- 651
- Women or men aged >= 18 years
- Patients with locally advanced or metastatic, histologically documented TNBC by central testing (absence of human epidermal growth factor 2 [HER2], oestrogen receptor [ER], and progesterone receptor [PR] expression), not amenable to surgical therapy
a. HER2 negativity is defined as either of the following by central laboratory assessment: IHC 0, IHC 1+ or IHC2+/in situ hybridisation (ISH) as per American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline (ISH- is defined as a ratio of HER2 to CEP17 <2.0)
b. ER and PR negativity are defined as <1% of cells expressing hormonal receptors via IHC analysis as per ASCO-CAP guideline
- Eligible for taxane monotherapy
- No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC. Prior radiation therapy for metastatic disease is permitted. Previous chemotherapy for early breast cancer is permitted if completed >=12 months before randomization
- Availability of formalin-fixed paraffin-embedded tumour block (preferred) or at least 17 unstained slides, collected <=3 months prior to randomisation, with an associated pathology report, if available. If a tumour sample taken within 3 months before randomisation is not available and a tumour biopsy is not clinically feasible, the primary surgical resection sample or the most recent FFPE tumour biopsy sample may be used. Of these additional options, the most recent sample should be used.
a. The tumor tissue should be of good quality based on total and viable
tumor content and must be evaluable prospectively for PD-L1 expression via central testing. Tumor specimens not suitable for evaluation of PD-L1 expression include fine needle aspiration, brushing, cell pellet from pleural effusion, tumor tissue from bone metastases and lavage samples - Eastern Cooperative Oncology Group performance status of 0 or 1 - Life expectancy >=12 weeks - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - Adequate haematologic and end-organ function test results within 2 weeks prior to the first study treatment - Negative human immunodeficiency virus (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 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 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. - Women of child bearing potential must agree to either use a contraceptive method with a failure rate of <=1% per year or to remain abstinent during the treatment period and for at least 5 months after the last dose of atezolizumab/placebo, or for at least 6 months after the last dose of paclitaxel - Women of child bearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug - For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm, as defined in the protocol
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 480
F.1.3 Elderly (>=65
Cancer-Specific Exclusion Criteria:
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to randomization
- Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met:
a. Measurable disease outside the CNS
b. Metastases are limited solely to cerebellar and supratentorial lesions
c. No ongoing requirement for corticosteroids as therapy for CNS disease
d. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
e. No evidence of progression or haemorrhage after completion of CNS directed therapy
Note: Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible if all other criteria above are met
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites (Note: patients with indwelling catheters are allowed)
- Uncontrolled tumour-related pain
- Uncontrolled hypercalcemia or clinically significant (symptomatic) hypercalcemia
- Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
General Medical Exclusion Criteria:
- Pregnant or lactating women, or intending to become pregnant during the study
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
- Presence of an abnormal electrocardiogram (ECG) that is clinically significant
- Serious infection requiring antibiotics within 2 weeks prior to randomization, including but not limited to infections requiring hospitalization or IV antibiotics- Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
- Treatment with investigational therapy within 30 days prior to initiation of study treatment
- Inability to understand the local language(s) for which the Patient Reported Outcome (PRO) questionnaires are available
Exclusion Criteria Related to Study Treatment:
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the atezolizumab formulation
- History of hypersensitivity reactions to paclitaxel or other drugs formulated in the same solvent as paclitaxel (polyoxyethylated castor oil)
- History of autoimmune disease
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
- Current treatment with anti-viral therapy for HBV
- Active tuberculosis
- Receipt of a
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