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

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-

Related coverage on Hipa.ai

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By research site
Indiana University Health Hospital· Indianapolis, INIndiana University Melvin and Bren Simon Cancer Center· Indianapolis, INOhio State University· Columbus, OHUniversity of Pennsylvania· Philadelphia, PA

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