Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05155033
Other study ID # 10000354
Secondary ID 000354-C
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 18, 2022
Est. completion date September 1, 2027

Study information

Verified date June 3, 2024
Source National Institutes of Health Clinical Center (CC)
Contact NCI SB Immunotherapy Recruitment Center
Phone (866) 820-4505
Email irc@nih.gov
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Background: Aldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer. Objective: To learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer. Eligibility: Adults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma. Design: Participants will be screened with: - Medical history - Physical exam - Electrocardiogram - Blood and urine tests - Ability to perform tasks of daily living - Imaging scans (CT, MRI, PET, and/or X-rays). They may get a contrast agent to enhance the images. - Photographs, if needed Some of these tests will be repeated during the study. Participants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course. About 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits. Participation will last for 5 years.


Description:

Background: High-dose interleukin-2 was approved by the FDA for the treatment of metastatic melanoma and renal cell carcinoma, with overall response rates of 15-16%. Complete regression of disease was seen in 6-7% of participants with many long-term durable responses. The regimen has not been widely adopted due to complexities in management and the development of alternative effective therapies, such as monoclonal antibodies targeting immune checkpoints (ipilimumab, pembrolizumab, nivolumab) or small molecule inhibitors. Pembrolizumab was approved by the FDA for the treatment of metastatic melanoma based on a series of studies demonstrating objective response rates from 21-34%. There remains a considerable population of participants with disease that never responded to treatment, in addition to participants with short durations of response prior to recurrence. There has been limited clinical investigation of the combination of interleukin-2 and pembrolizumab. The hypothesis under investigation is that non-specific activation of the immune system with both positive stimulation (aldesleukin) and release of negative regulation (pembrolizumab) may have meaningful clinical impact for participants with limited therapeutic options. Objectives: Primary: To determine the objective response rate as determined by RECIST 1.1 criteria to combined aldesleukin and pembrolizumab in participants with advanced melanoma refractory to anti-PD-1 therapy and treatment-refractory metastatic renal cell carcinoma Secondary: To determine progression free survival with the combined regimen To determine the toxicity profile of this treatment regimen To determine the objective response rate as determined by RECIST 1.1 criteria to combined aldesleukin and pembrolizumab in participants with treatment-na(SqrRoot) ve advanced melanoma Exploratory: To evaluate clinical and laboratory correlates of response To perform immunologic correlative studies of peripheral blood, tumor, and/or tumor infiltrating lymphocytes including but not limited to phenotype and functional analysis of longitudinal samples Eligibility: Participants must be/have: Age >= 18 years of age. ECOG performance status of 0 or 1. Expected survival of greater than 6 months. Histologically or cytologically confirmed melanoma or renal cell cancer, as follows: Cohort 1: Metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy. Cohort 2: Metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1/PDL1 based therapy. Cohort 3: Metastatic or advanced locoregional melanoma not amenable to curative surgical resection na(SqrRoot) ve to anti-PD-1 therapy. No allergies or hypersensitivity to high-dose aldesleukin or pembrolizumab administration. No concurrent major medical illnesses or any form of immunodeficiency. No history of Grade 3/4 immune-related adverse events affecting major organ systems associated with the administration of single agent pembrolizumab or nivolumab. Design: Study treatment will be given in two courses. A course shall consist of two cycles (each 21 days) of treatment. Cycles in Course 1 shall consist of pembrolizumab (200 mg IV) infusion on the morning of Day 1 with aldesleukin (IL-2) administration (600,000 IU/kg intravenous bolus every eight hours) to begin later that day. IL-2 will be administered to tolerance or to a maximum of 10 doses. A second cycle of treatment will begin during Week 4 (Day 22-28). Approximately two months from the beginning of therapy, participants will be evaluated for response including physical exam, clinical laboratory testing, and cross-sectional imaging. Participants that do not demonstrate progressive disease will receive a second course of pembrolizumab alone, if clinically appropriate. Participants with stable disease will be monitored until disease progression (every 3 months x 3) up to one year. Participants with an objective response will be monitored until disease progression (every 3 months x 3, every 6 months x 8) up to five years.


Recruitment information / eligibility

Status Recruiting
Enrollment 78
Est. completion date September 1, 2027
Est. primary completion date September 1, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility - INCLUSION CRITERIA: - Participants must have histologically or cytologically confirmed cancer that falls into one of three cohorts: (1) metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy; (2) metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1/PDL1 based therapy; (3) metastatic or advanced locoregional melanoma not amenable to curative surgical resection and naive to anti-PD-1 therapy. - Participants must have measurable disease (per RECIST v1.1 criteria), metastatic melanoma or renal cell cancer. - Age >=18 years of age. - Clinical performance status of ECOG 0 or 1. - Willing to practice birth control from the time of enrollment on this study and for four months after treatment. - Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. - Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) - Seronegative for hepatitis B antigen and for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. - Participants must have adequate organ and marrow function as defined below: - ANC > 1000/mm^3 without the support of filgrastim - WBC >= 3000/mm^3 - Platelet count >= 100,000/mm^3 - Hemoglobin > 8.0 g/d (Subject may be transfused to reach this cut-off) - Serum ALT/AST <= 5.0 x ULN - Serum creatinine <= 1.6 mg/dL - Total bilirubin <= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL. - More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment. Note: Participant may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to <= grade 1. - Ability of subject to understand and the willingness to sign a written informed consent document. - Willing to sign a Durable Power of Attorney Form. - Subject must be co-enrolled on protocol 03-C-0277 EXCLUSION CRITERIA: - Participant is breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. - Concurrent systemic steroid therapy. - Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses. - Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS). - History of major organ autoimmune disease. - Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1 monotherapy, including but not limited to myocarditis, pneumonitis, colitis, and hepatotoxicity. - Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.) - History of severe immediate hypersensitivity reaction to pembrolizumab or aldesleukin. - History of coronary revascularization or ischemic symptoms. - For select participants with a clinical history prompting cardiac evaluation: last known LVEF <= 45%. - For select participants with a clinical history prompting pulmonary evaluation: known FEV1 <= 50%. - Participant is receiving any other investigational agents.

Study Design


Intervention

Drug:
Pembrolizumab
Pembrolizumab 200 mg IV over approximately 30 minutes on Day 1 of cycles 1 and 2 during Courses 1 and 2.
Aldesleukin
Aldesleukin (IL-2) administration [600,000 IU/kg IV bolus every 8 hours continuing for up to 4 days (maximum 10 doses)] starting on Day 1 of cycles 1 and 2 during Course 1.

Locations

Country Name City State
United States National Institutes of Health Clinical Center Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Response rate in treatment refractory disease Determine the rate of objective response (using RECIST v1.1 criteria) 8 weeks after Course 1 Cycle 1 then after Course 2, every 3 months x 3 (up to one year), every 6 months x 8 (up to five years)
Secondary Progression Free Survival Elapsed duration from enrollment to progression of disease Every 2-6 months for up to 5 years
Secondary Response rate in treatment naive melanoma Determine the rate of objective response (using RECIST v1.1 criteria) 8 weeks after Course 1 Cycle 1 then after Course 2, every 3 months x 3 (up to one year), every 6 months x 8 (up to five years)
Secondary Safety and tolerance Using standard CTCAE 5.0 First dose through 30 days after last treatment
See also
  Status Clinical Trial Phase
Active, not recruiting NCT02224781 - Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma Phase 3
Active, not recruiting NCT05470283 - Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma Phase 1
Recruiting NCT05388877 - E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma Phase 1
Active, not recruiting NCT05103891 - Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations Phase 1
Completed NCT00414765 - Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma Phase 4
Completed NCT02857270 - A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer Phase 1
Completed NCT01621490 - PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma Phase 1
Recruiting NCT05779423 - Cryoablation+Ipilimumab+Nivolumab in Melanoma Phase 2
Active, not recruiting NCT04940299 - Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma Phase 2
Active, not recruiting NCT02278887 - Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma Phase 3
Active, not recruiting NCT02360579 - Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma Phase 2
Terminated NCT02521870 - A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Phase 1/Phase 2
Completed NCT02177110 - A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma
Withdrawn NCT01340729 - Open-Label Study of TPI 287 for Patients With Metastatic Melanoma Phase 1/Phase 2
Withdrawn NCT01416844 - Study of Immune Responses in Patients With Metastatic Melanoma Phase 2
Terminated NCT01468818 - Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma Phase 2
Completed NCT00984464 - Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma Phase 2
Completed NCT00631618 - Clinical Trial of Sutent to Treat Metastatic Melanoma Phase 2
Terminated NCT00571116 - Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy Phase 1
Recruiting NCT00226473 - Standard Palliative Care Versus Standard Palliative Care Plus Polychemotherapy in Metastasized Malignant Melanoma Phase 4