Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer

NCT ID: NCT03111901

Last Updated: 2019-07-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-29
• Study Completion Date: 2023-10-31

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.

Conditions

Carcinoma, Renal Cell; Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab solution

Interleukin-2

Intervention Type: DRUG

Interleukin-2 solution

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab solution

Interleukin-2

Intervention Type: DRUG

Interleukin-2 solution

Interventions

Pembrolizumab

Pembrolizumab solution

Intervention Type: DRUG

Interleukin-2

Interleukin-2 solution

Intervention Type: DRUG

Other Intervention Names

MK-3475; KEYTRUDA; IL-2

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

William Grosh, MD

OTHER

Sponsor Role: lead

Responsible Party

William Grosh, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

William W Grosh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia Health System

Locations

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

18537

Identifier Type: -

Identifier Source: org_study_id