Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer
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|ClinicalTrials.gov Identifier: NCT03308396|
Recruitment Status : Recruiting
First Posted : October 12, 2017
Last Update Posted : September 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Kidney Cancer Kidney Cancer Clear Cell Renal Cell Carcinoma||Drug: Guadecitabine Drug: Durvalumab||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||58 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase Ib/II|
|Masking:||None (Open Label)|
|Official Title:||Single Arm Phase Ib/II Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer: Big Ten Cancer Research Consortium BTCRC-GU16-043|
|Actual Study Start Date :||December 19, 2017|
|Estimated Primary Completion Date :||December 1, 2019|
|Estimated Study Completion Date :||December 1, 2020|
Experimental: Single Arm
This is a non-randomized, single arm, open label Phase Ib/II study.
Days 1-5 Guadecitabine (at Ph II dose)
Day 8 Durvalumab (1500 mg IV) Day 8 Durvalumab (1500 mg IV)
Days 1-5 Dose 0: 60 mg/m^2 Dose -1: 45 mg/m^2
Other Name: SGI-110
Day 8 Durvalumab (1500 mg IV)
Other Name: MEDI4736
- Phase Ib: Dose limiting toxicities will be assessed to determine if the trial is stopped before the Phase II portion. [ Time Frame: 28 days/First cycle ]Number of patients with dose-limiting toxicity (DLT) of the combination of durvalumab and guadecitabine
- Objective response rate [ Time Frame: 1 year ]Objective response rate (complete response (CR) + partial response (PR)) by RECIST 1.1 in Cohort 1
- Phase II: Overall Survival (OS) [ Time Frame: 2 years ]will be reported with 95% confidence intervals from the Kaplan-Meier estimates.
- Phase II: Duration of Response (DoR) [ Time Frame: 2 years ]will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.
- Phase II: Progression-free survival (PFS) [ Time Frame: 2 years ]will be assessed using Kaplan-Meier estimates including the 95% confidence band separately for cohort 1 and for cohort 2.
- Phase II: Clinical benefit rate (CBR) [ Time Frame: 2 years ]reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
- Phase II: Complete response (CR) proportion [ Time Frame: 2 years ]reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
- Phase II: Objective Response Rate (ORR) [ Time Frame: 2 years ]reported as binomial proportions and corresponding 95% binomial confidence intervals separately for cohort 1 and cohort 2
- Phase II: Assess Adverse Events [ Time Frame: 2 years ]by CTCAE ver 4 including events of special interest such as immune mediated toxicities
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03308396
|Contact: Ahran Lee||317.634.5842 ext email@example.com|
|Contact: Ajjai Alva, M.D.||firstname.lastname@example.org|
|United States, Illinois|
|Univerisity of Illinois Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Erin Vidra 312-996-7902 email@example.com|
|Principal Investigator: David Peace, MD|
|United States, Iowa|
|University of Iowa Hosptials and Clinics||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Marian Anderson 319-353-4578 firstname.lastname@example.org|
|Principal Investigator: Yousef Zakharia, MD|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Ajjai Alva, M.D. 734-936-0091 email@example.com|
|Contact: Carolina Fernandez-Castillo 734-763-8373 firstname.lastname@example.org|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Daniel Bell 732-235-9850 email@example.com|
|Principal Investigator: Eric Singer, MD|
|United States, Pennsylvania|
|Penn State Cancer Institute||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: Sean Fleming 717-531-5364 firstname.lastname@example.org|
|Principal Investigator: Monika Joshi, MD|
|Study Chair:||Ajjai Alva, M.D.||University of Michigan|