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Renal Cell CarcinomaPhase 2NCT03501381

High Dose IL 2 and Entinostat in RCC

A Phase 2 study testing Entinostat and Interleukin-2 in people with Renal Cell Carcinoma, run by Roberto Pili at 5 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 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Entinostat and Interleukin-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
5 sitesUnited States
Study dates
24 May 2018to Apr 2024
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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
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  • 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
  • Total Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN
  • Lactate Dehydrogenase Within Normal Limits
  • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN
  • Females of childbearing potential must have a negative serum pregnancy test during screening and within 3 days prior to receiving first dose of study medication. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 90days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • Pulmonary: FEV1 > 2.0 liters or > 75% of predicted for height and age
  • Cardiac: 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. NOTE: 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.
  • CNS: No history of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases. NOTE: Patients with CNS metastases should have a head CT/MRI within 21 days prior to treatment initiation. Any imaging abnormality indicative of CNS metastases will exclude the patient from the study. Patients with previously excised/gamma knifed solitary or oligometastases and no evidence of recurrent disease for 6 months are eligible.

Who cannot join

  • 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
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  • 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%.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Hematology Oncology Clinic, LLC

    Baton Rouge, Louisiana, 70809

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Indiana Univeristy Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Univeristy of Southern California

    Los Angeles, California, 90033

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

Other trials in United States

About this study

Official title: A Phase II Randomized, Open Label Study of High Dose Interleukin 2 vs High Dose Interleukin 2 Plus Entinostat in Advanced Renal Cell Carcinoma

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.

Being tested
Entinostat, Interleukin-2
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.

  • EntinostatDrug

    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

  • Interleukin-2Drug

    Also called aldesleukin

    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.

Study groups in NCT03501381
Study groupRoleWhat they receive
High Dose Interleukin 2Active comparatorHD IL-2 600,000 IU/kg Every 8 hours on Days 1-5 and Days 15-19
Receives: Drug: Interleukin-2
High Dose Interleukin 2 plus EntinostatExperimentalHD 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
Receives: Drug: Entinostat; Drug: Interleukin-2

What is being measured

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

  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.

    Measured: 24 months

Secondary outcomes (4)

  1. Objective Response Rate

    Estimate and compare the objective response rate in patients receiving high dose interleukin 2 or high dose interleukin 2 plus entinostat. ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST 1.1.

    Measured: 24 months

  2. Assess Adverse Events

    Assess the safety and tolerability of high dose interleukin 2 plus entinostat using CTCAE v4

    Measured: 24 months

  3. Duration of response

    Assess duration of response in patients receiving high dose interleukin 2 or high dose interleukin 2 plus entinostat. Duration of overall response-the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).

    Measured: 24 months

  4. Overall Survival

    Assess overall survival in patients receiving high dose interleukin 2 or high dose interleukin 2 plus entinostat. Overall survival is defined by the date of randomization to date of death from any cause.

    Measured: 24 Months

Timeline

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

  1. First posted18 Apr 2018
  2. Study start24 May 2018
  3. Primary completion20 Jan 2023
  4. Study completionApr 2024 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03501381
Sponsor's protocol ID
HCRN GU17-289
Status last verified
Aug 2023
First submitted
10 Apr 2018
Last updated
1 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Entinostat and Interleukin-2 in people with Renal Cell Carcinoma, run by Roberto Pili at 5 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 25 inclusion and 15 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 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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?

Progression Free Survival (PFS) (time frame: 24 months). 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 NCT03501381.

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 1 Sep 2023.

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