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

Melanoma Clinical Trial

— UVA-AM-002  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03111901
• Other study ID #: 18537
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: October 29, 2018
• Est. completion date: October 2023

Study information

• Verified date: July 2019
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Melanoma

Intervention

Drug:
• Pembrolizumab
Pembrolizumab solution
• Interleukin-2
Interleukin-2 solution

Locations

Country	Name	City	State
United States	University of Virginia Cancer Center	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
William Grosh, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: adverse event profile	Obtain preliminary data on the safety of LD-IL2 with pembrolizumab	up to 90 days post-treatment
Primary	Disease control rate: melanoma	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)
Primary	Disease control rate: renal cell cancer	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	Progression free survival: metastatic melanoma	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.
Secondary	Progression free survival: renal cell cancer	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.