Anti-PD-1 +/- RT for MSI-H Solid Tumors
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|ClinicalTrials.gov Identifier: NCT04001101|
Recruitment Status : Recruiting
First Posted : June 27, 2019
Last Update Posted : July 2, 2021
|Condition or disease||Intervention/treatment||Phase|
|Microsatellite Instability High Mismatch Repair Deficiency Colorectal Cancer||Combination Product: RT and Anti-PD-1 Drug: Anti-PD-1||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Masking Description:||In an effort to minimize bias, the study will utilize a randomization. The randomization list will be generated by the study biostatistician and provided only to the study personnel who will be responsible for assigning each subject to a cohort of the study.|
|Official Title:||A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors|
|Actual Study Start Date :||October 10, 2019|
|Estimated Primary Completion Date :||April 5, 2023|
|Estimated Study Completion Date :||April 2024|
Active Comparator: RT and Anti-PD-1
In the pembrolizumab + RT arm, pembrolizumab will be started on study within 7 days (+/- 7 days) of start of RT.
Pembrolizumab will be given as standard of care in both arms
Combination Product: RT and Anti-PD-1
limited metastatic site radiation
Placebo Comparator: Anti-PD-1
anti-PD-1 therapy alone Pembrolizumab will be given as standard of care in both arms
anti-PD-1 therapy alone
- Out-of-field ORR improvement [ Time Frame: 12 months ]• Out-of-field objective response rate (ORR: CR+PR) according to RECIST 1.1 assessment
- in-field tumor control and disease control [ Time Frame: 12 Months ]In-field tumor control and disease control will be defined as SD, PR, or CR, of the target lesion, by RECIST 1.1 criteria
- Determine the chronology and profile of the radiation-associated immune response. [ Time Frame: 12 months ]The University of Colorado School of Medicine Human Immune Monitoring Shared Resource (HIMSR) will quantify peripheral CD8, CD4, and regulatory T cell populations and characterize the relative functional state of these cells using activation markers (CD45RO, ICOS, and CD25) and inhibitory markers (TIM-3, CTLA-4, LAG-3, and PD-1). The HIMSR will also characterize peripheral dendritic cells (pDCs, CD1c+, and CD141+ subsets), monocytes (classical and non-classical subsets), myeloid-derived suppressor cells (MDSCs, granulocytic and monocytic subsets), and expression of activation (CD80 and HLA-DR) and inhibitory molecules (PDL1) on these cells. Further, cytokine production by NK cells, B cells, T cells, and monocytes will be measured by flow cytometry after brief ex-vivo stimulation. The HIMSR will also perform a protein multiplex array of 40 potential biomarkers in plasma.
- Durability of disease response [ Time Frame: 12 months ]In patients that achieve an objective response to pembrolizumab +/- RT, durability of response will be measured from the initiation of pembrolizumab until PD.
- Progression-free Survival [ Time Frame: 12 months ]Progression-free survival will be measured from the date of initiation of pembrolizumab to the time of tumor progression or death from any cause for one year.
- Overall Survival [ Time Frame: 12 Months ]Overall survival will be measured from the date of initiation of pembrolizumab to the time of death from any cause for one year.
- Quality of life score [ Time Frame: 12 Months ]Quality of life questionnaire, 28 questions rating experience from 1 to 4 (4 being "very much", 1 being "not at all") and two questions rating overall health and quality of life on a scale from 1 to 7 (7 being excellent)
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): NCT04001101
|Contact: Robyn Swingemail@example.com|
|Contact: Christine Fisher, MDfirstname.lastname@example.org|
|United States, Colorado|
|University of Colorado Hospital||Recruiting|
|Denver, Colorado, United States, 80045|
|Contact: Suzanne Withrow 720-848-0593 email@example.com|
|Principal Investigator: Christine Fisher, MD|