Triple Negative Breast Neoplasms
Conditions
Interventions
Atezolizumab group (Experimental): Atezolizumab + Gemcitabine/Carboplatin or Capecitabine
Atezolizumab will be administered, 1200 mg by Intravenous (IV) infusion with Gemcitabine 1000 mg/m2, followed
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Carboplatin
Capecitabine
Placebos
Administration, Oral
Atezolizumab
Sponsors
Roche Servicios S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed triple negative breast cancer(TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic 2. Documented disease progression occurring within 12 months from the last treatment with curative intent 3. Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. 4. Prior radiation therapy for recurrent disease is permitted 4. Measurable or non-measurable disease, as defined by RECIST 1.1 5. Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumour block (preferred) or at least 25 unstained slides with an associated pathology report, if available 6. Eastern Cooperative Oncology Group performance status 0-1 7. Life expectancy = 12 weeks 8. Adequate haematologic and end-organ function 9. Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening 10. 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 11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. 12. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of =1% per year during the treatment period and for at least 5 months after the last dose of study treatment 13. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm
Exclusion criteria
Exclusion criteria: 1. 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 > 2 weeks prior to randomisation 2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. 3. Symptomatic or rapid visceral progression 4. No prior treatment with an anthracycline and taxane 5. History of leptomeningeal disease 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed) 7. Uncontrolled tumour-related pain 8. Uncontrolled or symptomatic hypercalcemia 9. Malignancies other than TNBC within 5 years prior to randomisation) 10. Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina 11. Presence of an abnormal ECG 12. Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. 13. Current treatment with anti-viral therapy for HBV. 14. Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis 15. Treatment with investigational therapy within 28 days prior to randomisation 16. Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of study treatment Related to Atezolizumab: 17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins 18. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation 19. History of autoimmune disease 20. Prior allogeneic stem cell or solid organ transplantation 21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 22. Active tuberculosis 23. Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo 24. Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents 25. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation 26. Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomisation, or anticipated requirement for systemic immunosuppressive medications during the trial Related to Capecitabine: 27. Inability to swallow pills 28. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis 29. Kno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival-OS (Time form randomization until death from any cause). Measurement time: 30 months post First Patient In (FPI) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients alive 12 months. Measurement time: Randomization; 12 months post randomization 2. Proportion of patients alive 18 months. Measurement time: Randomization; 18 months post randomization 3. Progression-free survival-PFS (Time from randomization until to the first occurrence of disease progression or death. It will determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)). Measurement time: Randomization to the first occurrence of disease progression or death (through the end of study, approximately 36 months). 4. Objective response rate-ORR (Proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1). Measurement time: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until PD, withdrawal of consent, death, or study termination (approximately 36 months). 5. Duration of objective response-DoR (Time from the first occurrence of a documented objective response to disease progression or death Determined by the investigator according to RECIST 1.1). Measurement time: Through the end of study, approximately 36 months. 6. Clinical benefit rate-CBR (Proportion of patients with a complete response (CR), Partial Response (PR) or Stable Disease (SD) as determined by the investigator according to RECIST 1.1). Measurement time: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 36 months). 7. Time to deterioration (TTD) of the GHS / HRQoL, defined by a minimally significant decrease of =10 points on the GHS / HRQoL scale (points 29, 30) of the EORTC QLQ-C30 at two consecutive evaluations time points. 8. Average and average changes from the baseline point in the function (physical, emotional, social and cognitive function) and the sympto | — |
Countries
Algeria, Bosnia and Herzegovina, Brazil, Cuba, Finland, France, Germany, Humgary, Italy, Kazakhstan, Mexico, Morocco, Panama, Republic of Korea, Russian Federation, Serbia, Singapore, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactMaría Fernanda Manavella
F. Hoffmann-La Roche Ltd
Outcome results
None listed