Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer

Kidney Cancer Clinical Trial

Official title: Single Arm Phase Ib/II Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer: Big Ten Cancer Research Consortium BTCRC-GU16-043

Status Active, not recruiting

Clinical Trial Summary

This is a single arm, multi-centre (via Big Ten Cancer Research Consortium) phase Ib/II study of patients treated with durvalumab 1500 mg IV q 4 weeks in combination with guadecitabine at the recommended phase 2 dose subcutaneously for 5 consecutive days. Eligible patients will have metastatic RCC with a clear cell component, ECOG performance status of 0-1, have received 0-1 prior therapy but no prior anti-PD-1/PD-L1/CTLA4 (Cohort 1, 36 subjects). Study treatment could potentially continue for up to 13 cycles (52 weeks).

Clinical Trial Description

A total of up to 58 subjects will be enrolled on both phases.

Phase Ib: 6-12 subjects; enrolled into either Cohort 1 or 2. Phase II: 46 subjects; enrolled into either Cohort 1 or 2.

Cohort 1 (36 subjects): received 0-1 prior therapy and no prior anti-PD-1/PD-L1/CTLA4.

Cohort 2 (16 subjects): received up to 2 prior therapies, one of which must include an anti-PD-1/PD-L1 therapy to which they did not respond. Only one prior anti-PD-1/PD-L1 therapy is allowed.

Patients from Phase Ib treated at the eventual phase II dose will be combined with patients in Phase II in the efficacy analysis.

• Therapy will start with guadecitabine on days 1-5 of a 28-day cycle. Guadecitabine will be dosed subcutaneously on days 1-5 at either dose level 0 (60 mg/m2) or dose level -1 (45 mg/m2), based on the recommended phase II dose.

• Durvalumab will be started on day 8 of the 28-day cycle. Durvalumab will be administered intravenously at a flat dose of 1500mg every 28 days.

• Study treatment may continue for up to 13 cycles (52 weeks) in the absence of confirmed progression, intolerable toxicity, or withdrawal of consent.

Phase Ib Treatment Plan

• Dose limiting toxicities (DLTs) will be evaluated within the first cycle (i.e., within the first 28 days).

• Six patients will be enrolled at dose level 0. If 2 or fewer patients experience a dose limiting toxicity, the study will continue to the phase II portion at dose level 0.

• Alternately, if 3 or more patients have a dose limiting toxicity at dose level 0, 6 patients will be accrued at the lower dose (dose -1). If 2 or fewer patients experience a dose limiting toxicity, the study will continue to phase II at dose level -1.

• If 3 or more subjects experience a dose limiting toxicity at dose level -1, the treatment will be considered unsafe and the trial will be stopped. In this case, durvalumab and guadecitabine will be permanently discontinued and the subjects followed per protocol. ;

Related Conditions & MeSH terms

• Advanced Kidney Cancer
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Kidney Cancer
• Kidney Neoplasms

• NCT number: NCT03308396
• Study type: Interventional
• Source: Big Ten Cancer Research Consortium
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 19, 2017
• Completion date: December 2023