Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03308396|
Recruitment Status : Active, not recruiting
First Posted : October 12, 2017
Last Update Posted : March 16, 2021
|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)|
|Actual Enrollment :||57 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 :||May 1, 2021|
|Estimated Study Completion Date :||December 1, 2021|
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03308396
|United States, Illinois|
|Univerisity of Illinois Cancer Center|
|Chicago, Illinois, United States, 60612|
|United States, Iowa|
|University of Iowa Hosptials and Clinics|
|Iowa City, Iowa, United States, 52242|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, Pennsylvania|
|Penn State Cancer Institute|
|Hershey, Pennsylvania, United States, 17033|
|Study Chair:||Ajjai Alva, M.D.||University of Michigan|