A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With HER2-Positive Locally Advanced or Metastatic Breast Cancer who Have Received Prior Trastuzumab and Taxane Based Therapy.
- Conditions
- nresectable locally advanced or metastatic breast cancer (MBC).MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004189-27-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 202
- Age >=18 years
- Archival tumor samples must be obtained from primary and/or metastatic sites
- Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression
- Human epidermal growth factor-2 positive breast cancer (BC) as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of >=2.0 for the number of HER2 gene copies to the number of chromosome 17 copies, prospectively tested by a Sponsor- designated central laboratory prior to enrollment. Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility
- Histologically or cytologically confirmed invasive BC incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic breast cancer
- Prior treatment for BC in the adjuvant, unresectable locally advanced or metastatic settings which must include both, a taxane and trastuzumab (alone or in combination with another agent)
- Progression must have occurred during or after most recent treatment for locally advanced BC/MBC or within 6 months after completing adjuvant therapy
- Participants must have measurable disease that is evaluable as per RECIST v1.1
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and end-organ function as evidenced by the following local laboratory results obtained within 2 weeks prior to the first study treatment (Cycle 1, Day 1):
• Absolute neutrophil count >=1500 cells/microliter (µL) (without granulocyte-colony stimulating factor support) within 2 weeks prior to Cycle 1, Day 1
• Platelet count >=100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin >=9.0 gram/deciliter (g/dL)
• Albumin > 2.5 g/dL
• Aspartate aminotransferase, alanine transaminase, and alkaline phosphatase <= 2.5 × the upper limit of normal (ULN)
• Total bilirubin <=1.5 × the ULN
• International normalized ratio and activated partial thromboplastin time <=1.5 × the ULN
• Calculated creatinine clearance >= 30 millilitre/min
- Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause
- For women of childbearing potential, agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of trastuzumab emtansine or 5 months after the last dose of atezolizumab/placebo, whichever is later. Women must refrain from donating eggs during this same period.
- For men, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm that together result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose trastuzumab emtansine.
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 200
- Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death 1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1, except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria
- Radiation therapy within 2 weeks prior to Cycle 1, Day 1
- History of exposure to the cumulative doses of anthracyclines
- History of other malignancy within the previous 5 years
- Cardiopulmonary dysfunction
- Patients with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Current severe, uncontrolled systemic disease
- Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
- Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
- Need for current chronic corticosteroid therapy
- 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 randomization
- Participants with known central nervous system disease
- Leptomeningeal disease
- Symptomatic pleural effusion, pericardial effusion, or ascites
- Uncontrolled hypercalcemia (>1.5 millimol/litre ionized calcium or calcium > 12 milligram/dL or corrected serum calcium greater than the ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Current Grade >= 3 peripheral neuropathy
- History of autoimmune disease and idiopathic pulmonary fibrosis
- Prior allogeneic stem cell or solid organ transplantation
- Active tuberculosis
- Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
- Treatment with systemic immunostimulatory agents
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications
- Breastfeeding, or intending to become pregnat during the study.
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