Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer
Phase I/II Study of High Dose Interleukin 2, Aldesleukin, in Combination With the Histone Deacetylase Inhibitor Entinostat in Patients With Metastatic Renal Cell Carcinoma
12 other identifiers
interventional
47
1 country
4
Brief Summary
This phase I/II trial studies the side effects and best dose of entinostat when given together with aldesleukin and to see how well this works in treating patients with kidney cancer that has spread to other places in the body. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Aldesleukin may stimulate the white blood cells to kill kidney cancer cells. Giving entinostat together with aldesleukin may be a better treatment for metastatic kidney cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2009
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 29, 2009
CompletedFirst Submitted
Initial submission to the registry
December 18, 2009
CompletedFirst Posted
Study publicly available on registry
December 24, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 22, 2019
CompletedResults Posted
Study results publicly available
February 24, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 12, 2027
ExpectedApril 13, 2026
February 1, 2026
9.6 years
December 18, 2009
August 7, 2020
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Dose-limiting Toxicities of Entinostat When Combined With Aldesleukin Within the Phase I
Number of dose-limiting toxicities of entinostat when combined with aldesleukin within the Phase I MEASUREMENT OF EFFECT Patients underwent CT scans at week 11 (+/- 7 days) of each cycle during aldesleukin administration and then every 8-12 weeks (+/- 2 weeks). Response Evaluation Criteria in Solid Tumors (RECIST V.1.0)
84 days
Overall Response Rate (Complete Plus Partial) (Phase II)
The proportion of patients who have a partial or complete response to treatment evaluated by RECIST V.1.0 criteria. MEASUREMENT OF EFFECT Patients underwent CT scans at week 11 (+/- 7 days) of each cycle during aldesleukin administration and then every 8-12 weeks (+/- 2 weeks). Response Evaluation Criteria in Solid Tumors (RECIST V.1.0)
Up to 12 months
Secondary Outcomes (7)
Incidence of Toxicity (Phase I)
84 days
Progression-free Survival
up to 12-months after the last subject enrolls
Overall Survival
up to 12-months after the last subject enrolls
Time-to-tumor Progression
up to 12-months after the last subject enrolls
Incidence of Toxicities
Up to 30 days
- +2 more secondary outcomes
Study Arms (1)
Treatment (entinostat, aldesleukin)
EXPERIMENTALPatients receive entinostat PO every 2 weeks beginning on day -14 and high-dose aldesleukin IV every 8 hours on days 1-5 and 15-19. Cycles repeat every 84 days\* in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients with evidence of tumor shrinkage may receive up to 3 cycles of high-dose aldesleukin therapy. Patients with stable disease by RECIST version 1.0 criteria, but without evidence of tumor shrinkage after two cycles will receive only entinostat until disease progression is documented.
Interventions
Given IV
Given PO
Undergo FDG-PET/CT
Undergo FDG-PET/CT
Undergo FDG-PET/CT
Eligibility Criteria
You may qualify if:
- 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 may have received up to two prior therapies including vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) and programmed cell death (PD)-1/PD ligand 1 (L1) inhibitors; 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
- Patients must have measurable or evaluable disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0
- Life expectancy of greater than 6 months
- Hemoglobin \>= 12 g/dL
- Leukocytes \>= 3,000/mm\^3
- Absolute neutrophil count \>= 1,500/mm\^3
- Platelets \>= 100,000/mm\^3
- Total bilirubin =\< 1.5 x laboratory upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x laboratory upper limit of normal
- Creatinine =\< 1.5 x laboratory upper limit of normal or calculated creatinine clearance of \>= 50 ml/min
- Lactate dehydrogenase (LDH) within normal limits (WNL)
- Corrected calcium =\< 10 mg/dL
- Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5
- +6 more criteria
You may not qualify if:
- Patients who have received more than two prior therapies
- Concurrent use of valproic acid is not allowed
- Patients may not be receiving any other investigational agents
- Patients with untreated central nervous system (CNS) metastases; patients should have a head CT/magnetic resonance imaging (MRI) within 28 days prior to treatment initiation; patients with previously excised/gamma knifed solitary or oligometastases and controlled disease are eligible
- 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 cerebrovascular accident (CVA) within 6 months, hypertension (defined as blood pressure of \> 160 mmHg systolic and/or \> 90 mmHg diastolic on medication) history of peripheral vascular disease, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with a history of allergy to entinostat or other medications that have a benzamide structure (i.e. tiapride, remoxipride, and clebopride)
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with entinostat
- Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- 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%
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Administrator, Compliance - Clinical Research Services
- Organization
- Roswell Park Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Saby George
Roswell Park Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 18, 2009
First Posted
December 24, 2009
Study Start
October 29, 2009
Primary Completion
May 22, 2019
Study Completion (Estimated)
February 12, 2027
Last Updated
April 13, 2026
Results First Posted
February 24, 2021
Record last verified: 2026-02