NCT03308396

Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: Ajjai Alva, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Guadecitabine	Days 1-5 Dose 0: 60 mg/m\^2 Dose -1: 45 mg/m\^2
DRUG	Durvalumab	Day 8 Durvalumab (1500 mg IV)

Timeline

• Start date: 2017-12-19
• Primary completion: 2022-12-01
• Completion: 2023-12-01
• First posted: 2017-10-12
• Last updated: 2022-02-17

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study