- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03552380
Study of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma
A Phase II Study to Evaluate the Safety, Pharmacodynamics, and Efficacy of Entinostat in Combination With Nivolumab Plus Ipilimumab in Patients With Renal Cell Carcinoma Previously Treated With Nivolumab Plus Ipilimumab
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20057
- Georgetown University
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana Univeristy Melvin and Bren Simon Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration.
- Histological or cytological evidence of renal cell carcinoma (initial diagnosis).
- Metastatic disease
- Progressive disease (PD) on nivolumab + ipilimumab regimen. Note: Patients who have completed at least one dose of ipilimumab + nivolumab and progress or have completed the 4 doses of ipilimumab + nivolumab and progress during nivolumab monotherapy maintenance are eligible unless they have received additional treatment(s) for their renal cell carcinoma prior to registration. Patients who discontinue prior ipilimumab + nivolumab or nivolumab monotherapy for toxicity are excluded. Patients who receive nivolumab or other anti-PD-1/PD-L1 agents as subsequent therapy after ipilimumab + nivolumab are excluded.
- Target lesions according to RECIST v1.1 or non-target bone lesions assessed by bone scan or positron emission tomography (PET) scan.
- A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off corticosteroids for ≥ 4 weeks, and are asymptomatic.
- Prior cancer treatment (excluding nivo/ipi) must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia or neuropathy) to ≤Grade 1 or baseline. If subject underwent major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration
- Platelets ≥100 x 109/L
- Absolute Neutrophil Count (ANC) ≥1.5 x 109/L
- Hemoglobin (Hgb) ≥9 g/dL or ≥5.6 mmol/L
- Creatinine OR Measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of CrCl) Creatinine clearance should be calculated per institutional standard ≤1.5 x the upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels >1.5 x institutional ULN
- Bilirubin ≤1.5 x ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) ≤3 x ULN
- Alanine aminotransferase (ALT) ≤3 x ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT/INR/PTT is within therapeutic range of intended use of anticoagulants
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and a negative urine pregnancy test within 3 days prior to first dose of study drug. If the screening serum test is done within 3 days prior to receiving the first dose of study drug, a urine test is not required.
- Women of childbearing potential must be willing to abstain from heterosexual intercourse or to use an effective method of contraception from the time of informed consent until 5 months after the last dose of study drug.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drugs and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 3 months after the last dose of entinostat.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
- Life expectancy of at least 6 months per investigator discretion.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including, but not limited to:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a corrected QT interval (QTc) interval > 470 msec.
- Uncontrolled hypertension or diabetes mellitus.
- Another known malignancy that is progressing or requires active treatment.
- Any prior history of other cancer within the prior 5 years with the exception of adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ).
- Active infection requiring systemic therapy.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Pregnant or breastfeeding. Note: breast milk cannot be stored for future use while the mother is being treated on study.
- Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
- Allergy to benzamide or inactive components of entinostat.
- Hypersensitivity to nivolumab, ipilimumab, or any of their excipients.
- Treatment with any investigational drug or device within 4 weeks prior to registration.
- Treatment with systemic steroids within 4 weeks prior to registration. Note: adrenal replacement doses of steroids (for example prednisone 10mg daily) are permitted while on study.
- Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
- Interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
- Diagnosis of immunodeficiency; or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 4 weeks prior to registration.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). Testing during screening is not required.
- Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative]). Subjects 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. HBV DNA test must be performed in these subjects prior to study treatment, and results must be negative to be eligible. Subjects with a history of hepatitis C must be tested for presence of hepatitis C virus (HCV) antibody. If HCV antibody positive, subjects will only be eligible if polymerase chain reaction is negative for HCV RNA.
- Has received a live vaccine within 30 days prior to planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Entinostat, Nivolumab and Ipilimumab
Entinostat: 5mg, 3mg, or 2mg orally (PO) on D1, 8, 15 plus Nivolumab: 3 mg/kg IV D1 and Ipilimumab 1 mg/kg IV D1 Each cycle is 21 days |
RP2D will be determined with a 6 patient safety lead-in.
Entinostat will continue until disease progression or prohibitive toxicity.
Cycles 1-4 are 21 day cycles.
Cycles 5 and subsequent are 14 day cycles.
Other Names:
Nivolumab will continue until disease progression or prohibitive toxicity.
Cycles 1-4 are 21 day cycles.
Cycles 5 and subsequent are 14 day cycles.
Other Names:
Ipilimumab will be administered in combination with entinostat and nivolumab for Cycles 1-4 only.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Establish the recommended Phase II dose (RP2D)
Time Frame: 6 months
|
The Safety Lead-In will be Entinostat tested in 6-subject cohorts with a dose de-escalation design (5 mg, 3 mg and 2 mg) in combination with fixed dose nivolumab and ipilimumab.
|
6 months
|
Objective Response Rate (ORR) via RECIST 1.1
Time Frame: 24 months
|
Assess ORR via RECIST 1.1 during the Phase II study of entinostat in combination with nivolumab and ipilimumab in subjects with metastatic RCC who have progressed on nivolumab + ipilimumab regimen.
ORR is defined as the rate of complete response (CR) + partial response (PR).
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assess Adverse Events
Time Frame: 24 months
|
Assess adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4
|
24 months
|
ORR via irRC
Time Frame: 24 months
|
Assess ORR via immune related response criteria (irRC) during the Phase II study of entinostat in combination with nivolumab and ipilimumab in subjects with metastatic RCC who have progressed on nivolumab + ipilimumab regimen.
ORR is defined as the rate of complete response (irCR) + partial response (irPR).
|
24 months
|
Progression Free Survival (PFS) via RECIST 1.1
Time Frame: 24 months
|
PFS per RECIST 1.1 is defined from day 1 of treatment until disease progression or death as a result of any cause, with progression defined per RECIST 1.1
|
24 months
|
Progression Free Survival (PFS) via irRC
Time Frame: 24 months
|
PFS per irRC is defined from day 1 of treatment until disease progression or death as a result of any cause, with progression defined per irRC.
|
24 months
|
Overall Survival (OS)
Time Frame: 24
|
OS is defined from Day 1 of treatment until death as a result of any cause
|
24
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Roberto Pili, MD, Indiana Univervisty Simon Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Histone Deacetylase Inhibitors
- Nivolumab
- Ipilimumab
- Entinostat
Other Study ID Numbers
- HCRN GU17-326
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Renal Cell Carcinoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Australian and New Zealand Urogenital and Prostate...RecruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11.2 Translocation-Related Renal Cell CarcinomaAustralia
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell CarcinomaUnited States
-
Bradley A. McGregor, MDBristol-Myers Squibb; ExelixisRecruitingRenal Cell Carcinoma | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Collecting Duct Renal Cell Carcinoma | Translocation Renal Cell Carcinoma | Unresectable Advanced Renal Cell Carcinoma | Metastatic Ncc Renal Cell CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell CarcinomaUnited States, Taiwan, Australia
-
Jonsson Comprehensive Cancer CenterBeiGene; Driven To CureWithdrawnMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8 | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Unresectable Renal Cell Carcinoma | Hereditary Leiomyomatosis and Renal Cell Carcinoma | Clear Cell Papillary Renal Neoplasm | Hereditary Papillary Renal Cell Carcinoma and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingChromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma | Fumarate Hydratase Deficient Renal Cell Carcinoma | Succinate Dehydrogenase Deficient Renal Cell Carcinoma | Collecting Duct Renal...United States
-
Australian and New Zealand Urogenital and Prostate...Bristol-Myers SquibbActive, not recruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11 Translocation CarcinomaAustralia
-
Peloton Therapeutics, Inc.Active, not recruitingKidney Cancer | Renal Cell Carcinoma | Renal Cancer | Renal Cell Carcinoma (RCC) | Renal Cell Cancer Metastatic | Kidney | Clear Cell Renal Cell Carcinoma (ccRCC) | Renal Cell Carcinoma Recurrent | Renal Cell Cancer, RecurrentUnited States
-
AmgenCompletedRenal Cell Carcinoma | Clear Cell Renal Cell Carcinoma | Clear Cell Renal Carcinoma | Renal Cell AdenocarcinomaFrance, United States, Germany
Clinical Trials on Entinostat
-
Sidney Kimmel Comprehensive Cancer Center at Johns...National Cancer Institute (NCI)CompletedMyelodysplastic Syndromes | Leukemia | Multiple Myeloma and Plasma Cell Neoplasm | Myelodysplastic/Myeloproliferative DiseasesUnited States
-
Hetty CarrawayActive, not recruitingAcute Myeloid LeukemiaUnited States
-
National Institutes of Health Clinical Center (CC)National Cancer Institute (NCI)Completed
-
University Hospital HeidelbergGerman Cancer Research CenterRecruitingSolid Tumor | CNS TumorFrance, Germany, Australia, Austria, Sweden, Netherlands, Switzerland
-
Abramson Cancer Center at Penn MedicineCompletedColorectal CancerUnited States
-
Syndax PharmaceuticalsPfizer; Merck KGaA, Darmstadt, GermanyCompletedStudy of Avelumab With or Without Entinostat in Participants With Advanced Epithelial Ovarian CancerFallopian Tube Cancer | Epithelial Ovarian Cancer | Peritoneal CancerUnited States
-
Syndax PharmaceuticalsMerck Sharp & Dohme LLCCompletedMelanoma | Non-Small Cell Lung Cancer | Mismatch Repair-Proficient Colorectal CancerUnited States
-
National Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Burkitt Lymphoma | Recurrent Adult Diffuse Large Cell Lymphoma | Recurrent Adult Diffuse Mixed Cell Lymphoma | Recurrent Adult Diffuse Small Cleaved Cell Lymphoma and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedStage IV Colon Cancer | Stage IV Rectal Cancer | Recurrent Colon Cancer | Recurrent Rectal CancerUnited States
-
Abramson Cancer Center of the University of PennsylvaniaSyndax PharmaceuticalsWithdrawn