Spots Global Cancer Trial Database for Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer

Study Description

Brief 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.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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