Study to assess the efficacy and safety of the study drug atezolizumab in combination with paclitaxel and bevacizumab in patients with previously untreated advanced or metastatic triple negative breast cancer.
- Conditions
- Advanced or metastatic triple-negative breast cancerMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001503-20-IT
- Lead Sponsor
- MEDICA SCIENTIA INNOVATION RESEARCH, ARO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 100
1. Signed ICF prior to participation in any study-related activities
2. Male or female patients=18 years at the time of signing ICF
3. Ability to comply with the study protocol, in the investigator's judgment
4. Histologically confirmed TNBC –regardless of PD-L1 status– per ASCO/CAP criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as <1% expression for ER and PgR as determined by IHC,and negative for HER2 (0–1+ by immunohistochemistry [IHC] or 2+ and negative by ISH test)
5. Unresectable locally advanced or metastatic disease documented by CT scan or MRI that is not amenable to resection with curative intent
6. No prior chemotherapy and/or targeted therapy and/or immunotherapy and/or antiangiogenic agent for MBC. Patients who have received (neo)adjuvant taxane-based chemotherapy and/or immunotherapy and/or an antiangiogenic agent are required to have a DFI of at least 12months after completion of each of these treatments. For (neo)adjuvant non-taxane-based chemotherapy, a DFI of at least 6months is required
7. Resolution of all acute toxic effects of prior anti-cancer therapy to grade = 1 as determined by the NCI-CTCAE v.5.0
8. Evidence of measurable disease or non-measurable disease as per RECIST v.1.1. Patients with only bone lesions are also eligible
9. Willingness and ability to provide the most recent tumor biopsy since last progression from either metastatic or primary tissues at the time of the inclusion to perform exploratory studies. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee. An additional tumor biopsy from either metastatic or primary (only if metastatic biopsies cannot be obtained for inaccessible lesion or subject safety concern) tissues would be collected at disease progression or study termination whenever it is feasible
10. ECOG Performance Status of 0 or 1
11. Life expectancy of =12 weeks
12. Adequate hematologic and organ function within 14 days before the first study treatment on C1D1, defined by the following parameters:a.Hematological:i.WBC count >3.0x109/L; ii. ANC>1.5 X 109/L; iii. Lymphocyte count 0.5x109/L (500L); iv. Platelet count 75.0x109/L; v. Hemoglobin > 9.0g/dL b. Hepatic: Bilirubin =1.5 times ×ULN (=3xULN in the case of Gilbert's disease); AST and ALT= 2.5×ULN (in the case of liver metastases =5×ULN);ALP=2.5×ULN(=5×ULN in the case of liver and/or bone metastases). c. Serum albumin=2.5g/dL d. Renal: Serum creatinine<1.5×ULN or creatinine clearance=50 mL/min based on Cockcroft-Gault glomerular filtration rate estimation. No proteinuria by dipstick urinalysis (trace proteinuria is allowed). In cases of proteinuria at least 1+ by urinalysis, proteinuria should be less than 500mg by 24-h urine collection. e. Coagulation:For patients not receiving therapeutic anticoagulation: PTT or aPTT and INR=1.5×ULN.For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
13. Negative HIV test at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ¿ 200/¿L, and have an undetectable viral load.
14. Negative HBsAg test and negative total HBcAb tests at screening, or positive total HBcAb test followed by a negative HBV DNA test at screening. Current treatment with anti-viral therapy for HBV is not allowed.
15. Negative HCV antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at s
-Known active uncontrolled or symptomatic CNS metastases as indicated by clinical symptoms,cerebral edema,and/or progressive growth.Patients w/ a history of CNS metastases are eligible if meet following criteria:•Evidence of measurable disease or non-measurable disease as per RECIST v.1.1.•Patient has no history of intracranial hemorrhage•Patient has not undergone stereotactic radiotherapy within 7days prior to initiation of study treatment, whole-brain radiotherapy within 14days prior to initiation of study treatment, or neurosurgical resection within 28days prior to initiation of study treatment•Patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted
-History of leptomeningeal disease
-Uncontrolled tumor-related pain
-Active or history of autoimmune disease or immune deficiency
-Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
-Uncontrolled or symptomatic hypercalcemia (ionized calcium>1.5mmol/L; calcium>12mg/dL)
-History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
-Active tuberculosis
-Significant cardiovascular disease 6months prior to initiation of study treatment. These include New York Heart Association Class II or greater cardiac disease, myocardial infarction, unstable arrhythmia, or unstable angina, symptomatic pericarditis, ventricular arrhythmias –except for benign premature ventricular contractions, arrhythmias or conduction abnormalities requiring a pacemaker or not controlled with medication, and prior peripheral vascular disease including any cerebrovascular accident including transient ischemic attack, any pulmonary embolism, any prior deep vein thrombosis, and/or any grade =2 peripheral vascular disease
-LVEF<50% as determined by MUGA scan or ECHO
-Uncontrolled hypertension (SBP greater than 160mmHg and DBP greater than 100mmHg)
-Major surgical procedure (defined as requiring general anesthesia) or significant traumatic injury within 28days of start of study drug, or patients who have not recovered from the side effects of any major surgery
-Concurrent malignancy(ies) or malignancy(ies) within 5years of study enrolment except for carcinoma in situ of the cervix, nonmelanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required
-Treatment with therapeutic oral or IV antibiotics or severe infection 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics are eligible for the study
-Prior allogeneic stem cell or solid organ transplantation
-Treatment w/ a live, attenuated vaccine within 4weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5months after the final dose of atezolizumab
-Extracranial radiotherapy or limited-field palliative radiotherapy within seven days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade=1
-Treatment w/ investigational therapy within 28days prior to initiation of study treatment
-Treatment w/ systemic immunosuppressive medication within 2weeks prior to initiation of treatment (including, but not limited to,corticosteroids,cyclophosphamide,azathioprine, methotre
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