Celecoxib, Recombinant Interferon Alfa-2b, and Rintatolimod in Treating Patients With Colorectal Cancer Metastatic to the Liver
|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: NCT03403634|
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : February 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Carcinoma in the Liver Recurrent Colorectal Carcinoma Stage IV Colorectal Cancer AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7||Drug: Celecoxib Other: Laboratory Biomarker Analysis Biological: Recombinant Interferon Alfa-2b Drug: Rintatolimod||Phase 2|
I. To determine the impact of a chemokine-modulatory regimen on the immune microenvironment of colorectal liver metastases, specifically the changes in the ratio between cytotoxic T-lymphocyte (CTL) marker (CD8a gene expression) to regulatory T cell (Treg) markers (FoxP3 gene expression).
I. Estimate the objective response rate of a chemokine-modulatory regimen in metastatic colorectal cancer (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
II. Examine the safety and tolerability profile of the combination of recombinant interferon alfa-2b (interferon alpha-2b), rintatolimod, and celecoxib when given as chemokine modulation to colorectal cancer patients prior to surgical resection using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
- Estimate the median progression free survival of a chemokine-modulatory regimen in metastatic colorectal cancer
- Estimate overall survival in participants with recurrent and/or metastatic unresectable colorectal cancer who received the chemokine-modulatory regimen
- Comparison (using RT-PCR, immunofluorescence [IF] and immunohistochemistry [IHC] on serial sections) of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of FoxP3 cells, and the expression of chemokine receptors on CD4+ and CD8+ T cells (CXCR3, CCR5, CCR4, CCR6, and CXCR4)
- Evaluate the local expression of effector T cells (Teff)-attracting chemokines (CCR5, CXCL9, CXCL10 and CXCL11) and Treg-favoring chemokines (CCL22 and CXCL12) using IF and RT-PCR.
Patients receive celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes, and rintatolimod IV QD on days 1, 2,3,8,9,10,15,16 and 17 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 12 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver|
|Actual Study Start Date :||April 19, 2018|
|Estimated Primary Completion Date :||March 1, 2020|
|Estimated Study Completion Date :||December 1, 2020|
Experimental: Treatment (celecoxib, interferon alfa-2b, rintatolimod)
Patients receive celecoxib orally PO BID, recombinant interferon alfa-2b IV QD over 20 minutes, and rintatolimod IV QD on days 1, 2, 3, 8, 9, 10, 15, 16 and 17 in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Biological: Recombinant Interferon Alfa-2b
- Change in tumor-infiltrating lymphocytes (TILs) in the colorectal cancer lesions [ Time Frame: Baseline up to 12 months ]The TILs will be summarized by time-point (pre-/post-treatment) using the mean, median, standard deviation; and graphically using dot-plots. A 90% confidence interval for the mean change in TILs will be obtained using standard methods.
- Incidence of adverse events according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months ]Safety profile will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment.
- Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 [ Time Frame: Up to 12 months ]Will be treated as binary data and summarized using frequencies and relative frequencies; with the ORR estimated using a 90% confidence interval obtained using Jeffrey's prior method.
- Progression free survival [ Time Frame: From the start of treatment until disease progression (defined by RECIST 1.1) or last-follow-up, assessed up to 12 months ]Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
- Overall survival [ Time Frame: From the start of treatment until death due to any cause or last follow-up, assessed up to 12 months ]Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
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): NCT03403634
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Sarbajit Mukherjee 800-765-9355 AskRoswelI@roswellpark.org|
|Principal Investigator: Sarbajit Mukherjee, MD|
|Principal Investigator:||Sarbajit Mukherjee, MD||Roswell Park Cancer Institute|