Aldesleukin and Pembrolizumab in Treating Patients With Advanced or Metastatic Kidney Cancer
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|ClinicalTrials.gov Identifier: NCT03260504|
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : November 5, 2019
|Condition or disease||Intervention/treatment||Phase|
|Clear Cell Renal Cell Carcinoma Stage III Renal Cell Cancer Stage IV Renal Cell Cancer||Biological: Aldesleukin Biological: Pembrolizumab||Phase 1|
I. To evaluate the safety and tolerability of aldesleukin (IL-2) combined with pembrolizumab (MK-3475) in patients with metastatic clear cell renal cell carcinoma (RCC).
I. To assess preliminary antitumor activity of pembrolizumab in combination with IL-2.
I. To investigate the association of PD-L1 protein expression by pretreatment tumor with response to treatment.
II. To investigate the association of regulatory T cell (Treg) frequency and Treg to effector T cell (Teff) ratios in peripheral blood and tumor tissue with response to therapy.
III. To investigate the association of de novo serological and cellular responses against the ubiquitous RCC tumor antigen 5T4 with response to therapy.
IV. To investigate the association of tumor infiltrating lymphocyte (TIL) repertoire clonality with response to therapy and to assess the detection of dominant TIL clones within peripheral blood over time in responding patients.
V. To investigate the association of whole genome copy number alterations measured on pretreatment archived, formalin fixed, paraffin embedded (FFPE) tumor with response to therapy.
OUTLINE: This is a dose-escalation study of aldesleukin.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive aldesleukin subcutaneously (SC) weekly on days 1-5 of courses 1 and 2 or aldesleukin IV on days 2-6 of courses 1 and 2. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for every 3 months for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Interleukin-2 (Aldesleukin) and Pembrolizumab Combination Therapy for Patients With Advanced Renal Cell Carcinoma|
|Actual Study Start Date :||August 28, 2018|
|Estimated Primary Completion Date :||March 17, 2021|
|Estimated Study Completion Date :||March 17, 2021|
Experimental: Treatment (pembrolizumab, aldesleukin)
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive aldesleukin SC weekly on days 1-5 of courses 1 and 2 or aldesleukin IV on days 2-6 of courses 1 and 2. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Given SC or IV
- Incidence of adverse events [ Time Frame: Up to 1 year ]Assessed by NCI Common Terminology Criteria for Adverse Events (NCI CTCAE)
- Anti-tumor activity [ Time Frame: At baseline and every 3 months for up to 1 year ]Tumor imaging post-treatment compared to baseline imaging; assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Overall response rate (ORR) [ Time Frame: At baseline and every 3 months for up to 1 year ]Assessed by RECIST 1.1
- Disease control rate (DCR) [ Time Frame: At baseline and every 3 months for up to 1 year ]Assessed by RECIST 1.1.
- Progression free survival (PFS) [ Time Frame: Up to 1 year ]PFS will be evaluated using the method of Kaplan-Meier. Median PFS times and associated 95% confidence interval will also be calculated
- Change in performance status [ Time Frame: At baseline and every 3 months for up to 1 year ]Assessed by Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Absolute numbers of effector T cells (Teff) [ Time Frame: Up to 1 year ]Will assess the ratio of Treg and Teff. Analyses of T cell subsets will be correlated with clinical outcomes.
- Absolute numbers of regulatory T cells (Treg) [ Time Frame: Up to 1 year ]Will assess the ratio of Treg and effector T cells. Analyses of T cell subsets will be correlated with clinical outcomes.
- Chromosomal copy number alterations [ Time Frame: Up to 1 year ]OncoScan chromosomal array analyses will be carried out on archived tumor for RCC patients treated with IL-2 and pembrolizumab and chromosomal numerical abnormalities (CNAs) correlated to objective response rate.
- De novo 5T4 specific humoral and/or cellular immune responses [ Time Frame: Up to 1 year ]Will be analyzed as a potential marker of "on target" effective anti-tumor immunity and correlated with clinical response.
- PD-L1 expression [ Time Frame: Up to 1 year ]Will be assessed by immunohistochemistry.
- Tumor infiltrating lymphocytes (TIL) clonality score [ Time Frame: Up to 1 year ]TIL clonality score will be correlated with clinical outcomes of renal cell carcinoma (RCC) patients treated with IL-2 plus pembrolizumab.
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): NCT03260504
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Scott S. Tykodi 206-667-3799 firstname.lastname@example.org|
|Principal Investigator: Scott S. Tykodi|
|Principal Investigator:||Scott Tykodi||Fred Hutch/University of Washington Cancer Consortium|