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Clear Cell Renal Cell CarcinomaPhase 1/2NCT01038778

Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer

A Phase 1/2 study testing Aldesleukin, Computed Tomography and Entinostat in people with Clear Cell Renal Cell Carcinoma and Metastatic Kidney Carcinoma, run by National Cancer Institute (NCI) at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, Computed Tomography and Entinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
4 sitesUnited States
Study dates
29 Oct 2009to 12 Feb 2027
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be < 1000 mg
  • Forced expiratory volume in 1 second (FEV1) >= 2.0 liters or >= 75% of predicted for height and age; (pulmonary function tests [PFTs] are required for patients over 50 or with significant pulmonary or smoking history)
  • No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina; patients who are over 40 or have had previous myocardial infarction greater than 6 months prior to entry will be required to have a negative or low probability cardiac stress test for cardiac ischemia
  • No history of cerebrovascular accident or transient ischemic attacks
  • The effects of entinostat on the developing human fetus at the recommended therapeutic dose are unknown; for this reason Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men with female partners of child bearing potential must also agree to use adequate contraception
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • 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%

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of high dose interleukin 2 (aldesleukin) in combination with entinostat in patients with metastatic renal cell carcinoma (RCC). (Phase I) II. To monitor toxicity and estimate the efficacy of high dose aldesleukin combined with entinostat in patients with metastatic RCC. (Phase II)

SECONDARY OBJECTIVES:

  1. To compare the time-to-tumor progression, progression-free survival and overall survival of patients with metastatic RCC treated with high dose aldesleukin combined with entinostat to the historical data of patients treated with high dose aldesleukin alone. (Phase II) II. To assess the toxicity of high dose aldesleukin combined with entinostat. (Phase II) III. To evaluate entinostat pharmacodynamics (PD) in blood and tumor samples. (Phase II) IV. To measure the association between baseline laboratory parameters (e.g. cluster of differentiation [CD]4+, CD8+, CD4+/forkhead box P3 [Foxp3]), tumor blood metabolism, and a variety of response variables (e.g. toxicity, response and survival). (Phase II) V. To explore the relationship between entinostat exposure with PD endpoints (e.g. toxicity and histone acetylation in peripheral blood mononuclear cells or peripheral blood mononuclear cells [PBMNCs] and changes in T cell subset population). (Phase II) VI. To evaluate the modulation of tumor metabolism by fluorodeoxyglucose (FDG, fludeoxyglucose F 18) positron emission tomography (PET)/computed tomography (CT) scan. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of entinostat followed by a phase II study.

Patients receive entinostat orally (PO) every 2 weeks beginning on day -14 and high-dose aldesleukin intravenously (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 Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria, but without evidence of tumor shrinkage after two cycles will receive only entinostat until disease progression is documented.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Being tested
Aldesleukin, Computed Tomography, Entinostat, Fludeoxyglucose F-18, Laboratory Biomarker Analysis
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo FDG-PET/CT

  • EntinostatDrug

    Also called HDAC inhibitor SNDX-275, MS 27-275, MS 275, MS-275

    Given PO

  • Fludeoxyglucose F-18Radiation

    Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18

    Undergo FDG-PET/CT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo FDG-PET/CT

Study groups in NCT01038778
Study groupRoleWhat they receive
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.
Receives: Biological: Aldesleukin; Procedure: Computed Tomography; Drug: Entinostat; Radiation: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 84 days

  2. 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)

    Measured: Up to 12 months

Secondary outcomes (7)

  1. Incidence of Toxicity (Phase I)

    Count of participants with grade 4 toxicity. The frequency and grade of toxicities will be tabulated for each dose level.

    Measured: 84 days

  2. Progression-free Survival

    The median progression-free survival (PFS) was estimated using standard Kaplan-Meier methods, where estimates of the median were obtained with 95% confidence intervals (CIs). PFS was defined as the time from the start of treatment to progression or death due to any cause or last follow-up, patients who did not progress or die were censored.

    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)

    Measured: up to 12-months after the last subject enrolls

  3. Overall Survival

    The 3-year overall survival (OS) rate was estimated using standard Kaplan-Meier methods, where estimates of the median were obtained with 95% confidence intervals (CIs). OS was defined as the time from the start of treatment to death due to any cause or last follow-up, patients who did not die were censored.

    Measured: up to 12-months after the last subject enrolls

  4. Time-to-tumor Progression

    The median time to tumor progression (TTP) was estimated using standard Kaplan-Meier methods, where estimates of the median were obtained with 95% confidence intervals (CIs). TTP was defined as the time from the start of treatment to progression or last follow-up. Patients that did not progress were censored.

    Measured: up to 12-months after the last subject enrolls

  5. Incidence of Toxicities

    The number of participants with serious adverse events.

    Measured: Up to 30 days

  6. Changes in the Level of Specific T Lymphocytes

    Mean percent change from baseline of T lymphocytes.

    Measured: Baseline to approximately 4 weeks post-treatment, up to 1 year

  7. Changes in Tumor Metabolisms by FDG Positron Emission Tomography (PET)/Computed Tomography (CT) Scan

    For binary predictors, the sensitivity and specificity with 95% confidence intervals will be reported. T tests will be used to compare the mean change between responders and non-responders. If there are sufficient numbers of responders, partial responders and non-responders an ANOVA will be used to compare changes in these three groups. If complete data are obtained for CD4+CD25^hi T cells at multiple time points post treatment, repeated measures ANOVA will be performed to evaluate data for trends over time.

    Measured: Baseline to approximately 5 weeks post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2009 (estimated)
  2. Study start29 Oct 2009
  3. Primary completion22 May 2019
  4. Study completion12 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01038778
Sponsor's protocol ID
NCI-2012-02900
Other IDs
NCI-2012-02900, CDR0000662915, I 145208, 7870, 7870, P30CA016056, R21CA137649, U01CA062505
Status last verified
Aug 2026
First submitted
18 Dec 2009
Last updated
13 Aug 2026
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aldesleukin, Computed Tomography and Entinostat in people with Clear Cell Renal Cell Carcinoma and Metastatic Kidney Carcinoma, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicities of Entinostat When Combined With Aldesleukin Within the Phase I (time frame: 84 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01038778.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.

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