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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03111901
Recruitment Status : Withdrawn (funding was withdrawn)
First Posted : April 13, 2017
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
William Grosh, MD, University of Virginia

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Melanoma Drug: Pembrolizumab Drug: Interleukin-2 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low-dose Interleukin-2 and Pembrolizumab Among Patients With Metastatic Melanoma and Renal Cell Carcinoma
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023


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:
  • MK-3475
  • KEYTRUDA

Drug: Interleukin-2
Interleukin-2 solution
Other Name: 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:
  • MK-3475
  • KEYTRUDA

Drug: Interleukin-2
Interleukin-2 solution
Other Name: IL-2




Primary Outcome Measures :
  1. Safety: adverse event profile [ Time Frame: up to 90 days post-treatment ]
    Obtain preliminary data on the safety of LD-IL2 with pembrolizumab

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03111901


Locations
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United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
William Grosh, MD
Investigators
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Principal Investigator: William W Grosh, MD University of Virginia Health System

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Responsible Party: William Grosh, MD, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT03111901     History of Changes
Other Study ID Numbers: 18537
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by William Grosh, MD, University of Virginia:
pembrolizumab
IL-2
interleukin-2
MK-3475
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Pembrolizumab
Interleukin-2
Antineoplastic Agents, Immunological
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs