Atezolizumab in Combination With Entinostat and Bevacizumab in Patients With Advanced Renal Cell Carcinoma

Part of paid clinical trials in Indianapolis, Indiana.

Sponsor
Roberto Pili
Study ID
NCT03024437
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — DRUG
    Atezolizumab will be given intravenously every 3 weeks at 1200 mg.
  • Bevacizumab — DRUG
    Bevacizumab will be given intravenously every 3 weeks at 15 mg/kg.
  • Entinostat — DRUG
    Entinostat will be given orally every 7 days at 1, 3, or 5 mg depending upon phase. In Phase I, dose levels will be tested in up to 3 cohorts starting at 1 mg. In Phase II, the dose will be the recommended phase II dose that was determined during Phase I (i.e., 1, 3, or 5 mg).

Study Details

This study will assess the immunomodulatory activity of entinostat in patients with advanced renal cell carcinoma receiving the PD-L1 inhibitor atezolizumab. The overall hypothesis is that entinostat will increase the immune response and anti-tumor effect induced by the PD-L1 inhibition by suppressing Treg function. We have chosen renal cell carcinoma that has been reported to respond to PD1/PD-L 1 inhibition. The schedule of entinostat is based on our previous experience with this agent. Based on our working hypothesis that low dose HDAC inhibitors will have a suppressive function on Tregs but not on T effector cells, the starting dose of entinostat will be 1 mg and will be escalated up to 5 mg rather than the 10 mg dose. The combination also with bevacizumab will provide an effective VEGF inhibition that may potentiate the immune response and anti-tumor effect induced by atezolizumab. The proposed dose and schedule for atezolizumab and bevacizumab has been shown to be well tolerated in prior Phase/I/II studies and is currently tested in a Phase III randomized study in patients with renal cell carcinoma with sunitinib as a control arm. The highest proposed dose level for entinostat (5 mg) represents 50% of the recommended Phase II dose for this compound as a single agent.

Key Dates

First listed
Jan 18, 2017
Start date
Jun 29, 2017
Status verified
Mar 2025
Primary completion
Jun 24, 2024
Completion
Jun 24, 2024

Study Design

Enrollment
31 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I - Dose Escalation
    Open to patients meeting eligibility criteria with advanced renal cell carcinoma and ANY or NO prior treatments. Three dose levels of entinostat will be tested in 3-patient cohorts according to the 3 + 3 standard design (1 mg, 3 mg and 5 mg). The starting dose level of entinostat will be 1 mg orally every 7 days. The Phase II dose will be recommended phase II dose of entinostat (i.e., the highest tested dose that is declared safe and tolerable by the Investigators and Sponsor).
  • Experimental: Phase II - Cohort A
    Open to patients meeting eligibility criteria with advanced renal cell carcinoma and NO prior treatments. Patients in Cohort A will be treated with atezolizumab, bevaciuzmab, and the recommended phase II dose of entinostat. During Phase II, the study will have a run-in period with entinostat for one cycle followed by atezolizumab and bevacizumab for the second cycle, and then the combination phase (i.e., atezolizumab + bevacizumab + entinostat for all cycles thereafter).
  • Experimental: Phase II - Cohort B
    Open to patients meeting eligibility criteria with advanced renal cell carcinoma and at least one prior treatment with a PD1 or PDL1 inhibitor. Patients in Cohort B will be treated with the same combination therapy as in Cohort A.

Primary Outcome Measure

Phase I: Recommended Phase II Dose of Entinostat [ Time Frame: 21 days ]

Locations (4)

FacilityCityStateZIPSite coordinators
Indiana University Health HospitalIndianapolisIndiana46202-
Indiana University Melvin and Bren Simon Cancer CenterIndianapolisIndiana46202-
Ohio State UniversityColumbusOhio43210-
University of PennsylvaniaPhiladelphiaPennsylvania19104-

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