High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03991130|
Recruitment Status : Recruiting
First Posted : June 19, 2019
Last Update Posted : August 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Stage Iv Renal Cell Carcinoma, Metastatic||Drug: IL-2 and Nivolumab||Phase 2|
PrimaryObjective Determine the overall response rate (complete response and partial response) for patients receiving anti-PD-1 (nivolumab) and high dose IL-2 (HD IL-2) in subjects with metastatic melanoma or renal cell carcinoma who have previously progressed on anti-PD-1 therapy. Response assessment will be performed using revised RECIST guideline (v 1.1).
- Characterize safety, tolerability and adverse effects (AE) profile of nivolumab with HD IL-2 in subjects with metastatic malignant melanoma or renal cell carcinoma
- Measure Progression-Free Survival (PFS) using RECIST 1.1 after completion of at least one course of therapy (2 doses of nivolumab, 2 cycles of HD IL-2) for subjects enrolled in the study.
- Correlate PD-L1 expression and tumor mutational burden (TMB) in archived diagnostic tumor tissue with best clinical response for subjects with metastatic melanoma and renal cell carcinoma
- Correlate myeloid-derived suppressor cells and T-cell subsets in peripheral blood during therapy with best clinical response (RECIST criteria) and treatment outcome in subjects with metastatic melanoma or renal cell carcinoma. Data will be collected prior to each treatment and after each course of treatment.
Study Duration: 48 months Amount of Subjects: up to 25 subjects
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma|
|Actual Study Start Date :||May 23, 2019|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||August 2024|
|Experimental: High Dose IL-2 and Nivolumab||
Drug: IL-2 and Nivolumab
Course length will be 35 days. Subjects will receive 480 mg IV of nivolumab on day 1 of the cycle. The patient will be admitted to UCSD Jacobs Medical center for standard HD IL-2 which will be administered every 8 hrs for up to 14 doses days 8-12 per institutional practice. The patient will be readmitted days 22-28 for HD IL-2 every 8 hrs for up to 14 doses. Nivolumab 480 mg IV will be administered day 35. Scans for response will occur 4 weeks after day 35 nivolumab dose and response will be determined by RECIST 1.1 to determine if the patient will receive the next course.
- Overall Response Rate [ Time Frame: 3 years post treatment ]The primary endpoint will be the response rate [complete response (CR) and partial response (PR)] of combined therapy with nivolumab and HD IL-2 in metastatic melanoma and renal cell carcinoma and will be evaluated using revised RECIST 1.1. Response rate will be computed with associated 95% confidence intervals.
- Drug Toxicity [ Time Frame: After Initiation of a 35 day study treatment period up to 90 days following the last administration of study treatment ]Proportion of subjects with each grade of adverse events as defined by CTCAE v 5.0 will be computed. Toxicity will be reported in a tabular and descriptive manner.
- Progression Free Survival [ Time Frame: 1 year +/- 3 months ]• Median PFS times will be calculate and PFS rate at 1 year +/- 3 months will be calculated with associated 95% confidence intervals based on the Kaplan-Meier method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03991130
|Contact: Gregory Daniels, MD, PhDemail@example.com|
|Contact: Jaren Mullenfirstname.lastname@example.org|
|United States, California|
|UC San Diego Moores Cancer Center||Recruiting|
|La Jolla, California, United States, 92093|
|Contact: Jaren Mullen 858-822-6176 email@example.com|
|Contact: Yael Cohen-Arazi 858-822-5354 firstname.lastname@example.org|
|Principal Investigator: Mina Nikanjam, MD, PhD|
|Sub-Investigator: Gregory A. Daniels, MD, PhD|