Ignite Creation Date:
2025-12-25 @ 3:01 AM
Ignite Modification Date:
2026-01-01 @ 5:21 AM
Study NCT ID:
NCT05155033
Status:
RECRUITING
Last Update Posted:
2025-08-11
First Post:
2021-12-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Status:
RECRUITING
Status Verified Date:
2025-08-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Detailed 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.
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.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 000354-C | None | None | View |