Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB in Advanced HER-2 Negative Breast Cancer

Sponsor
Centro Nacional de Investigaciones Oncologicas CARLOS III
Study ID
NCT02802098
Phase
EARLY_PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    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.
  • Bevacizumab — DRUG
    Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A)

Study Details

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.

Key Dates

Start date
May 31, 2016
Status verified
Jun 2020
Primary completion
Jun 30, 2019
Completion
Jul 31, 2019

Study Design

Enrollment
25 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE

Arms

  • 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.

Primary Outcome Measure

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 ]

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