High Dose IL 2 and Entinostat in RCC

NCT03501381 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU17-289
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, randomized, open label study of high dose interleukin 2 vs high dose interleukin 2 plus entinostat in clear cell RCC patients who are candidate for high dose interleukin 2. Patients will be randomized to ARM 1 (high dose interleukin 2 plus entinostat) or ARM 2 (high dose interleukin 2). Subjects will receive up to 3 courses of high dose interleukin 600,000 units/kg administered IV every 8 hrs on Days 1-5 and Days 15-19 (maximum 28 doses) +/- entinostat 5 mg orally given every 2 weeks starting on Day-14, continuously. Tumor response assessment will be performed between HD IL-2 courses.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Compare PFS between arms. PFS is defined as the time from date of randomization until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.

  24 months

Secondary Outcomes (4)

• Objective Response Rate

  24 months

• Assess Adverse Events

  24 months

• Duration of response

  24 months

• Overall Survival

  24 Months

Study Arms (2)

High Dose Interleukin 2

ACTIVE COMPARATOR

HD IL-2 600,000 IU/kg Every 8 hours on Days 1-5 and Days 15-19

Drug: Interleukin-2

High Dose Interleukin 2 plus Entinostat

EXPERIMENTAL

HD IL-2 600,000 IU/kg Every 8 hours on Days 1-5 and Days 15-19 plus Entinostat 5 mg orally every 2 weeks starting Day -14

Drug: Entinostat; Drug: Interleukin-2

Interventions

Entinostat DRUG

Entinostat should be taken 1-2 hours prior to the HD IL-2 infusion. Dose reductions for entinostat should be followed. Entinostat will continue after high dose IL-2 every 2 weeks

High Dose Interleukin 2 plus Entinostat

Interleukin-2 DRUG

In the event of clinical benefit after a course of HD IL-2 (stable disease or tumor shrinkage) patients will receive a second treatment course of HD IL-2 therapy. Patients with evidence of tumor shrinkage after the 2nd HD IL-2 treatment course may receive a 3rd treatment course of HD IL-2.

Also known as: aldesleukin

High Dose Interleukin 2; High Dose Interleukin 2 plus Entinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0 within 14 days prior to registration.
• Life expectancy of greater than 6 months.
• Patients must have pathological diagnosis of renal cell carcinoma that is metastatic or surgically unresectable. The histology must be clear cell carcinoma or predominant clear cell carcinoma.
• Patients must have measurable or evaluable disease by RECIST 1.1.
• Up to two prior therapies for RCC are allowed. One prior therapy must contain an immune checkpoint inhibitor.Prior palliative radiation to metastatic lesion(s) is permitted, provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated
• White blood cell (WBC) ≥ 3,000 K/mm3
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
• Leukocytes ≥ 3,000/mm3
• Platelets ≥ 100,000/mm3
• Hemoglobin (Hgb) ≥ 12 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Calculated creatinine clearance ≥ 50 mL/min
• Corrected calcium ≤ 10 mg/dL
• Urine protein \< 1 +; if ≥ 1+, a 24 hour urine protein should be obtained and be \< 1,000 mg

You may not qualify if:

• Prior treatment with HD IL-2
• Concurrent use of valproic acid use is not allowed.
• Receiving medications that can effect clotting ability: warfarin, aspirin (once-daily aspirin use- maximum dose 325 mg/day is permitted), nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents.
• Patients may not be receiving other investigational agents.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding
• Any prior history of other cancer within the prior 5 years with the exception of adequately treated basal cell carcinoma, cervical intraepithelial neoplasia \[CIN\]/cervical carcinoma in situ, melanoma in situ or ductal carcinoma in situ \[DCIS\], localized Gleason 6 prostate cancer, papillary thyroid cancer or other non-melanoma skin cancers.
• Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Association Class II, III, or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (\< the last 6 months), cardiac arrhythmia, history of CVA within 6 months, hypertension (defined as blood pressure of \>160 mmHg systolic and/or \>90 mmHg diastolic on medication), QTc interval \> 470 msec, history of peripheral vascular disease, uncontrolled diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study
• HIV-positive patients receiving combination antiretroviral therapy are are eligible if their HIV is well-controlled (undetectable VL and CD4 count \>350) and they are on anti-retrovirals unlikely to interact with entinostat.
• Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid \[qualitative\]). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. NOTE: HBV DNA test must be performed prior to study treatment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Serious or non-healing wound, ulcer or bone fracture.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 therapy.
• Anticipation of need for major surgical procedures during the course of the study.
• Left ventricular ejection function \< 45%.

Sponsors & Collaborators

• Roberto Pili: lead
• Indiana University Melvin and Bren Simon Cancer Center: collaborator
• Syndax Pharmaceuticals: collaborator
• Clinigen, Inc.: collaborator

Study Sites (5)

Univeristy of Southern California

Los Angeles, California, 90033, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Univeristy Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Hematology Oncology Clinic, LLC

Baton Rouge, Louisiana, 70809, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

entinostat; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Roberto Pili, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 18, 2018
• Study Start: May 24, 2018
• Primary Completion: January 20, 2023
• Study Completion: April 1, 2024
• Last Updated: September 1, 2023

Record last verified: 2023-08

Locations

US (5)