Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, (DURVA+ Study)

Malignant Solid Neoplasm Clinical Trial

Official title: DURVA+ : Evaluation of the Safety and Pharmacodynamics of Anti-PD-L1 Antibody Durvalumab in Combination With Chemotherapy in Patients With Advanced Solid Tumors

Status Recruiting

Clinical Trial Summary

This phase II trial studies the side effects of durvalumab when given together with chemotherapy in treating patients with solid tumors that have spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, capecitabine, carboplatin, paclitaxel, and 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. Giving chemotherapy with durvalumab may improve how immune cells respond and attack tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety of adding durvalumab to standard chemotherapy regimens.

SECONDARY OBJECTIVES:

I. Determine the changes that occur in the immune microenvironment in response to chemotherapy and assess how these changes alter the pharmacodynamic effects of a checkpoint inhibitor.

II. Investigate whether the response to immunotherapy correlates with patients' genetic aberrations and/or the activation status of tumor-infiltrating and circulating T cells.

III. Explore the relationship between immune status of the tumor and overall tumor mutational load.

IV. Assess preliminary antitumor activity of the durvalumab and chemotherapy combinations.

EXPLORATORY OBJECTIVE:

I. Assess whether changes in cell-free deoxyribonucleic acid (DNA) correlate with response or resistance to the study regimens.

OUTLINE: Patients are assigned to 1 of 7 arms.

ARM I: Patients receive durvalumab intravenously (IV) over 60 minutes on days 1 and 15 of cycles 1 and 2 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and durvalumab IV over 60 minutes on days 8 and 22 of cycles 1 and 2 and day 8 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who discontinue gemcitabine hydrochloride continue receiving durvalumab alone as in Arm I. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM III: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and durvalumab IV over 60 minutes on days 8 and 22 of cycles 1 and 2 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM IV: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14, and durvalumab IV over 60 minutes on days 8 of cycle 1, day 8 and 15 of cycle 2, day 8 of cycles 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM V: Patients receive carboplatin IV over 30-60 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 8 and 15 of cycle 2, day 8 of cycles 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM VI: Patients receive paclitaxel IV over 60 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 8 and 15 of cycle 2, day 8 of cycles 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

ARM VII: Patients receive nab-paclitaxel IV over 30 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 8 and 15 of cycle 2, day 8 of cycles 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

After completion of study treatment, patients are followed up monthly for 3 months. ;

Related Conditions & MeSH terms

• Malignant Solid Neoplasm

• NCT number: NCT03907475
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 2
• Start date: July 16, 2019
• Completion date: June 1, 2026