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

• ClinicalTrials.gov Identifier: NCT03111901
• Recruitment Status: Withdrawn
• First Posted: April 13, 2017
• Last Update Posted: July 12, 2019
• Sponsor: William Grosh, MD
• Information provided by (Responsible Party): William Grosh, MD, University of Virginia

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Locations

United States, Virginia

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

William Grosh, MD

Investigators

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

More Information

• Responsible Party: William Grosh, MD, Associate Professor of Medicine, University of Virginia
• ClinicalTrials.gov Identifier: NCT03111901
• Other Study ID Numbers: 18537
• First Posted: April 13, 2017
• Last Update Posted: July 12, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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