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RecruitingNCT03606967

Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine Vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer

Status
Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
70 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate the clinical response to nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine (Arm 1) versus (vs.) nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab (Arm 2) in patients with metastatic triple negative breast cancer (TNBC). SECONDARY OBJECTIVE: I. Evaluate the safety of nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine vs. nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab in patients with metastatic TNBC. EXPLORATORY OBJECTIVES: I. Assess the immune response induced by nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine vs. nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab in patients with metastatic TNBC. II. Biomarkers of response to therapy will be assessed based on the research biopsies performed at baseline, following the chemotherapy run-in (Part A) and following nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab +/- neoantigen vaccine (Part B). OUTLINE: PART A: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes and carboplatin IV over 30 minutes on days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 18 weeks (6 cycles) in the absence of disease progression or unacceptable toxicity. Patients who experience progression of disease or who are intolerant of treatment may switch and receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 of each remaining cycle or sacituzumab govitecan-hziy IV over 1-3 hours on days 1 and 8 of each remaining cycle. Treatment with nab-paclitaxel repeats every 28 days for up to 2 cycles (for patients with progressive disease) or until a total of 18 weeks of treatment have been completed (for patients who are intolerant of treatment) at the discretion of the treating physician. Treatment with sacituzumab govitecan-hziyl repeats every 21 days for up to 2 cycles (for patients with progressive disease) or until a total of 18 weeks of treatment have been completed (for patients who are intolerant of treatment) at the discretion of the treating physician. PART B: Patients are randomized to 1 of 2 arms. ARM I: Patients receive personalized synthetic long peptide vaccine and poly-ICLC subcutaneously (SC) on days 1, 4, 8, 15, 22, 50, and 78 in the absence of disease progression or unacceptable toxicity. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycles 1-4, durvalumab IV over 60 minutes on day 1 of each cycle and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive tremelimumab IV over 60 minutes on day 1 of cycles 1-4, durvalumab IV over 60 minutes on day 1 of each cycle and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, blood and urine sample collection, computed tomography (CT) scan and magnetic resonance imaging (MRI) on study. After completion of study treatment, patients are followed up every 3 months for 1 year, then annually thereafter.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo tumor biopsy
PROCEDUREBiospecimen CollectionUndergo blood and urine sample collection
DRUGCarboplatinGiven IV
PROCEDUREComputed TomographyUndergo CT scan
BIOLOGICALDurvalumabGiven IV
DRUGGemcitabine HydrochlorideGiven IV
PROCEDUREMagnetic Resonance ImagingUndergo MRI
DRUGNab-paclitaxelGiven IV
BIOLOGICALPersonalized Synthetic Long Peptide VaccineGiven SC
DRUGPoly ICLCGiven SC
BIOLOGICALSacituzumab GovitecanGiven IV
BIOLOGICALTremelimumabGiven IV

Timeline

Start date
2021-04-13
Primary completion
2026-12-30
Completion
2026-12-30
First posted
2018-07-31
Last updated
2026-04-17

Locations

30 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03606967. Inclusion in this directory is not an endorsement.