Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer (UVA-AM-002)

July 9, 2019 updated by: William Grosh, MD

Low-dose Interleukin-2 and Pembrolizumab Among Patients With Metastatic Melanoma and Renal Cell Carcinoma

This study will evaluate the safety and disease control rate of the combination of pembrolizumab plus low-dose interleukin-2 in patients who have either advanced melanoma or renal cell cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main Inclusion Criteria

  • Stage IV or unresectable stage III malignant melanoma or renal cell carcinoma.

  • Melanoma

    • Patients must have failed anti-PD-1/PD-L1 antibody therapy.
    • Patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab.
    • Patients may, but are not obligated, to have failed high- dose IL2.
    • BRAF status must be known or unable to be performed. If the melanoma expresses a BRAF mutation of V600E, V600K, or V600R patient must have received and progressed through a BRAF inhibitor or have failed that therapy due to toxicity.

  • Renal Cell Carcinoma

    • Patients must have failed anti-PD-1/PD-L1 antibody therapy.
    • Patients must have failed a VEGF pathway inhibitor and a second tyrosine kinase inhibitor.
    • Patients may, but are not obligated, to have failed high- dose IL2.
  • Measurable disease based upon RECIST 1.1.
  • Subjects with brain metastases will be eligible if the following are true:

  • Subjects with ≤ 3 brain metastases

    • All metastases are ≤ 3 cm
    • All metastases have been treated and are asymptomatic
    • Steroids are not required for management of the brain metastases
    • All metastases have been stable for 1 month following treatment

  • Subjects with > 3 brain metastases

    • All metastases are ≤ 3 cm
    • All metastases have been treated and are asymptomatic
    • Steroids are not required for management of the brain metastases
    • All metastases have been stable for 6 months following treatment
  • Performance status: ECOG 0-1.
  • Adequate organ function.
  • Ability to provide informed consent.

Main Exclusion Criteria:

  • Pregnancy
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of primary or secondary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 3 weeks prior to the first dose of trial treatment. Replacement doses of steroids are permitted.
  • Known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Known additional malignancies (exceptions DCIS or LCIS, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
  • Prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier.
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Known carcinomatous meningitis.
  • Active autoimmune disease that has required systemic treatment in the past 2 years. Patients may be eligible if they have the following autoimmune diseases: thyroiditis or hypothyroidism, mild arthritis, diabetes, resolved hypophysitis, ulcerative colitis after total abdominal colectomy.
  • Active infection requiring systemic therapy.
  • Known psychiatric or substance abuse disorders.
  • Known history of Human Immunodeficiency Virus (HIV).
  • Known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Severe chronic pulmonary disease.
  • Congestive heart failure, angina, or symptomatic cardiac arrhythmia or is classified according to the New York Heart Association classification as having Class III or IV heart disease.
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Level 1
Pembrolizumab (200 mg) administered intravenously (day 2 of cycle 1; day 1 of cycles 2 and beyond); Low dose-interleukin 2 (LD-IL2) 12 MIU/m2 administered subcutaneously (days 1-5 and 8-12 of each cycle); each cycle is 21 days.
Drug: Pembrolizumab
Pembrolizumab solution
Other Names:
  • KEYTRUDA
  • MK-3475
Drug: Interleukin-2
Interleukin-2 solution
Other Names:
  • IL-2
Experimental: Level -1
Pembrolizumab (200 mg) administered intravenously (day 2 of cycle 1; day 1 of cycles 2 and beyond); Low dose-interleukin 2 (LD-IL2) 5 MIU/m2 administered subcutaneously (days 1-5 and 8-12 of each cycle); each cycle is 21 days.
Drug: Pembrolizumab
Pembrolizumab solution
Other Names:
  • KEYTRUDA
  • MK-3475
Drug: Interleukin-2
Interleukin-2 solution
Other Names:
  • IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety: adverse event profile
Time Frame: up to 90 days post-treatment
Obtain preliminary data on the safety of LD-IL2 with pembrolizumab
up to 90 days post-treatment
Disease control rate: melanoma
Time Frame: baseline and every 9 weeks (up to week 104)
Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among candidate patients with metastatic melanoma treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment.
baseline and every 9 weeks (up to week 104)
Disease control rate: renal cell cancer
Time Frame: baseline and every 9 weeks (up to week 104)
Estimate the disease control rate (CR+PR+SD by RECIST 1.1) among patients with metastatic renal cell cancer treated with pembrolizumab and LD-IL2 and to determine whether disease control is significantly improved. SD for 6 months or more will be considered SD for the purpose of this assessment.
baseline and every 9 weeks (up to week 104)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival: metastatic melanoma
Time Frame: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.
Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first
From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.
Progression free survival: renal cell cancer
Time Frame: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.
Estimate progression-free survival defined as the duration of time from first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first
From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

William Grosh, MD

Investigators

  • Principal Investigator: William W Grosh, MD, University of Virginia Health System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 29, 2018

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

October 1, 2023

Study Registration Dates

First Submitted

March 23, 2017

First Submitted That Met QC Criteria

April 7, 2017

First Posted (Actual)

April 13, 2017

Study Record Updates

Last Update Posted (Actual)

July 12, 2019

Last Update Submitted That Met QC Criteria

July 9, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18537

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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