Phase II Clinical Trial to Evaluate the Efficacy and Safety of First Line Atezolizumab in Combination With Paclitaxel and Bevacizumab (Avastin®) in Patients With Advanced or Metastatic Triple-negative Breast Cancer

MedSIR26 sites in 5 countries100 target enrollmentOctober 5, 2020

ConditionsMetastatic Breast Cancer Advanced Breast Cancer Triple Negative Breast Cancer

InterventionsAtezolizumab Paclitaxel Bevacizumab

DrugsAtezolizumab Paclitaxel Bevacizumab

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: Metastatic Breast Cancer
Sponsor: MedSIR
Enrollment: 100
Locations: 26
Primary Endpoint: PFS (Progression-free Survival)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate to evaluate the efficacy and safety of first line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) in patients with advanced or metastatic triple-negative breast cancer (mTNBC)

Detailed Description

Men and women age ≥ 18 years with previously untreated unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) that is not amenable to resection with curative intent regardless of programmed death-ligand 1 (PD-L1) status. The number of patients to be included is 100 patients. The primary objective is to evaluate the efficacy -in terms of progression-free survival (PFS)- of first line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) in patients with unresectable locally advanced or metastatic TNBC. After signing the ICF and confirmed eligibility, patients will begin treatment on 28 days cycles: Atezolizumab (840 mg) intravenously on days 1 and 15; Paclitaxel (90 mg/m2) via IV infusion on days 1, 8 and 15; Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15. Patients will receive treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Patients discontinuing the study treatment will enter a post- treatment follow-up period until death, withdrawal of consent, patient is lost to follow-up, or study termination.

Registry

clinicaltrials.gov

Start Date

October 5, 2020

End Date

December 7, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

MedSIR

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed informed consent form (ICF) prior to participation in any study-related activities.
•Male or female patients ≥ 18 years at the time of signing ICF.
•Ability to comply with the study protocol, in the investigator's judgment.
•Histologically confirmed TNBC -regardless of PD-L1 status- per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PgR) as determined by immunohistochemistry (IHC), and negative for HER2 (0-1+ by immunohistochemistry \[IHC\] or 2+ and negative by in situ hybridization \[ISH\] test).
•Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
•No prior chemotherapy and/or targeted therapy and/or immunotherapy and/or antiangiogenic agent for triple negative MBC. Patients who have received (neo)adjuvant taxane-based chemotherapy and/or immunotherapy and/or an antiangiogenic agent are required to have a disease-free interval (DFI) of at least 12 months after completion of each of these treatments. For (neo)adjuvant non-taxane-based chemotherapy, a DFI of at least 6 months is required.
•Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia, grade ≤ 2 peripheral neuropathy, or other toxicities not considered a safety risk for the patient at investigator's discretion).
•Evidence of measurable disease or non-measurable disease as per RECIST v.1.
•Patients with only bone lesions are also eligible.
•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 will be collected as soon as possible at disease progression or study termination whenever it is feasible.

Exclusion Criteria

•Known active uncontrolled or symptomatic central nervous system (CNS) metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they meet the following criteria:
•Evidence of measurable disease or non-measurable disease as per RECIST v.1.
•The patient has no history of intracranial hemorrhage.
•The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
•The 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. Note 1: Patients requiring pain medication must be on a stable regimen at study entry.
•Note 2: Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Patients should be recovered from the effects of radiation.
•Active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis for a more comprehensive list of autoimmune diseases and immune deficiencies, with the following exceptions:
•Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.

Arms & Interventions

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

All eligible patients will be treated with atezolizumab (840 mg) intravenously on days 1 and 15, Paclitaxel (90 mg/m2) on days 1, 8 and 15 via IV infusion and Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15. Treatment cycles and patient visits are organized in scheduled cycles of 28 days.

Intervention: Atezolizumab

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

Intervention: Paclitaxel

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

Intervention: Bevacizumab

Outcomes

Primary Outcomes

PFS (Progression-free Survival)

Time Frame: 24 months

From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.