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

Stopped early · Phase 1/Phase 2

Conditions studied: Metastatic Cancer, Renal Cancer

In brief

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 facts

Study ID

NCT03024437

Run by

Roberto Pili

People needed

31

Starts

2017-06-29

Expected to finish

2024-06-24

Last updated by the study team

2025-03-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must meet the following criteria for study entry:
• Signed Informed Consent Form (ICF)
• Ability and willingness to comply with the requirements of the study protocol
• Age ≥ 18 years
• Measurable disease per RECIST v1.1 (see Appendix 4) for patients with solid malignancies or patients with bone disease must have disease evaluable by bone scan and/or PET scan
• Metastatic renal cell carcinoma
• o During Phase I - All prior treatments or none are allowed
• During Phase II/Cohort A - No prior treatments with PD1 or PDL1 inhibitors allowed
• During Phase II/Cohort B - Must have at least one prior treatment with a PD1 or PDL1 inhibitor for metastatic disease for at least 3 months and have progressed by either clinical or radiographic assessment
• Life expectancy of at least 6 months
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
• Absolute neutrophil count (ANC) ≥ 1500 cells/microL
• White blood cell (WBC) counts > 2500/microL
• Lymphocyte count ≥ 300/microL
• Platelet count ≥ 100,000/microL; for patients with hematologic malignancies, platelet count ≥ 75,000/microL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:
• Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
• Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN with the following exception: Patients with liver involvement: AST and/or ALT ≤ 5 x ULN
• Alkaline phosphatase (ALP) ≤ 2.0 x ULN with the following exception: Patients with documented liver involvement or bone metastases: ALP ≤ 5 x ULN
• Serum creatinine ≤ 1.25 x ULN or creatinine clearance ≥ 60 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
• (140 - age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)
• Urine dipstick for proteinuria < 2+ or 24-hour urine protein < 1 g of protein is demonstrated
• International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.

Where it is running

• Indiana University Health Hospital — Indianapolis, Indiana, United States
• Indiana University Melvin and Bren Simon Cancer Center — Indianapolis, Indiana, United States
• Ohio State University — Columbus, Ohio, United States
• University of Pennsylvania — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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