Pembrolizumab and Recombinant Interleukin-12 in Treating Patients With Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03030378|
Recruitment Status : Recruiting
First Posted : January 25, 2017
Last Update Posted : January 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Malignant Solid Neoplasm Unresectable Solid Neoplasm||Biological: Edodekin alfa Biological: Pembrolizumab||Phase 1|
I. Establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of edodekin alfa (recombinant human interleukin [rhIL]-12) in combination with pembrolizumab (MK-3475).
I. Evaluate the safety of the regimen by continuously monitoring adverse events that will be documented utilizing Common Terminology Criteria for Adverse Events (CTCAE) version (v).5.0.
II. Evaluate the overall response rate (Response Evaluation Criteria in Solid Tumors [RECIST] v.1.1) and the progression free survival of patients enrolled on the study.
III. Measure CD8+ T cell infiltration by immunohistochemistry in tumor biopsies obtained pre-treatment, after one week of rhIL-12 and after 2 cycles of pembrolizumab (MK-3475) in combination with rhIL-12.
I. Conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor, blood, and stool) obtained pre-treatment and during therapy.
OUTLINE: This is a dose-escalation study of recombinant interleukin-12.
Patients receive recombinant interleukin-12 subcutaneously (SC) on days 2, 5, 9, and 12 and pembrolizumab intravenously (IV) over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 2 year and then every 24 weeks for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Pembrolizumab (MK-3475) in Combination With Recombinant Interleukin-12 in Patients With Solid Tumors|
|Actual Study Start Date :||August 11, 2017|
|Estimated Primary Completion Date :||December 1, 2021|
|Estimated Study Completion Date :||December 1, 2021|
Experimental: Treatment (recombinant interleukin-12, pembrolizumab)
Patients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity.
Biological: Edodekin alfa
- Maximum tolerated dose [ Time Frame: Up to 5 years ]
- Recommended phase 2 dose [ Time Frame: Up to 5 years ]
- Incidence of adverse events [ Time Frame: Up to 30 days after last dose ]Adverse events will be tabulated by Common Terminology Criteria for Adverse Events (CTCAE) grade, CTCAE category, relatedness to treatment and dose level.
- Progression free survival [ Time Frame: From start of treatment to time of progression or death, whichever comes, first assessed up to 5 years ]The product-limit (Kaplan-Meier) progression-free survival function, with a 95% confidence region, will be determined for all patients and for patients treated at the MTD.
- Overall response rate [ Time Frame: From start of treatment until disease progression/recurrence ((taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 5 years ]Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. The proportion of patients experiencing confirmed overall (complete or partial) response will be calculated, as will a 95% exact (Klopper-Pearson) binomial confidence interval for all patients, and patients treated at the MTD (a confirmed clinical tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least >= 4 weeks apart.).
- CD8+ T cell infiltration [ Time Frame: Up to 2 cycles of treatment ]Will be assessed by immunohistochemistry. Will be compared to pre-treatment biopsy specimens by the Wilcoxon signed-rank test.
- Biomarker analysis [ Time Frame: Up to 5 years ]Will conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor, blood and stool) obtained at baseline and during therapy.
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): NCT03030378
|Principal Investigator:||Diwakar Davar||University of Pittsburgh Cancer Institute LAO|