Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB in Advanced HER-2 Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02802098|
Recruitment Status : Completed
First Posted : June 16, 2016
Last Update Posted : June 19, 2020
This is a single-arm pilot proof of concept, open-label clinical trial. Twenty-five subjects will be enrolled in 6 sites.
Metastatic breast cancer patients with disease progression to bevacizumab maintenance treatment will be potential candidates.
Bevacizumab maintenance will be considered as six weeks of bevacizumab treatment in monotherapy, with hormonal treatment or combined with chemotherapy in the context of previous bevacizumab plus chemotherapy regimens.
When progression to bevacizumab maintenance treatment occurs, patients will enter the trial and will start receiving DURVALUMAB 10 mg/kg Q2W IV infusion plus bevacizumab 10mg/kg IV infusion every 2 weeks. The patients will undergo a tumor biopsy before the first dose of DURVALUMAB, and after one month of combined treatment - the blood sampling will continue on a monthly basis. The treatment will continue until disease progression.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Bevacizumab-alone Maintenance Treatment Progression||Drug: Durvalumab Drug: Bevacizumab||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB (MEDI4736) in Advanced HER-2 Negative Breast Cancer: a Pilot Proof-of-concept Trial|
|Actual Study Start Date :||May 2016|
|Actual Primary Completion Date :||June 2019|
|Actual Study Completion Date :||July 2019|
Experimental: Bevacizumab + Durvalumab
Treatment with DURVALUMAB 10 mg/kg Q2W IV infusion plus Bevacizumab 10 mg/ Kg Q2W, IV infusion for a maximum duration of treatment of 12 months. Study treatment should be discontinued prior to 12 months if there is confirmed PD (unless the investigator considers the subject to continue to receive benefit from treatment), initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue study treatment occur.
Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 can be expressed by tumours to evade detection by the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks the PD-L1 interaction with PD-1, countering the tumour's immune-evading tactics.
Other Name: MEDI4736
Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A)
Other Name: Avastin
- To compare different peripheral blood mononuclear cells subpopulations at baseline or during treatment among patients showing benefit ro not from the combinations [ Time Frame: throughout the study up to progression disease, an average of 1 year ]Determine the immunodynamics changes from baseline in peripheral blood and in the tumor of combined administration of DURVALUMAB and the monoclonal antibody bevacizumab in advanced HER-2- negative breast cancer patients that have progressed to bevacizumab-based treatment. From baseline every 4 weeks throughout the study up to progression disease
- To determine progression-free survival of the combination [ Time Frame: up to 12 weeks ]Assessed by RECIST 1.1
- To determine overall survival [ Time Frame: up to death ]Overall survival rate by Kaplan-Meier Analysis
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Throughout study completion, an average of 1 year ]Evaluate safety and toxicity of combination of both DURVALUMAB and bevacizumab
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02802098
|Hospital Universitario de Fuenlabrada|
|Fuenlabrada, Madrid, Spain, 28942|
|H. Arnau de Vilanova Lleida|
|Lleida, Spain, 25198|
|Hospital Ramón y Cajal|
|Madrid, Spain, 28034|
|Hospital Universitario 12 de Octubre|
|Madrid, Spain, 28041|
|Madrid, Spain, 28223|
|Hospital General de Valencia|
|Valencia, Spain, 46014|