Regorafenib, Ipilimumab and Nivolumab for the Treatment of Chemotherapy Resistant Microsatellite Stable Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT04362839|
Recruitment Status : Recruiting
First Posted : April 27, 2020
Last Update Posted : May 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Colon Adenocarcinoma Metastatic Colon Adenocarcinoma Metastatic Colorectal Adenocarcinoma Metastatic Colorectal Carcinoma Metastatic Rectal Adenocarcinoma Stage III Colon Cancer AJCC v8 Stage III Rectal Cancer AJCC v8 Stage IIIA Colon Cancer AJCC v8 Stage IIIA Rectal Cancer AJCC v8 Stage IIIB Colon Cancer AJCC v8 Stage IIIB Rectal Cancer AJCC v8 Stage IIIC Colon Cancer AJCC v8 Stage IIIC Rectal Cancer AJCC v8 Stage IV Colon Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IV Rectal Cancer AJCC v8 Stage IVA Colon Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVA Rectal Cancer AJCC v8 Stage IVB Colon Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVB Rectal Cancer AJCC v8 Stage IVC Colon Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Stage IVC Rectal Cancer AJCC v8||Biological: Ipilimumab Biological: Nivolumab Drug: Regorafenib||Phase 1|
I. To determine the recommended dose level of the combination of regorafenib, nivolumab and ipilimumab in patients with advanced metastatic colorectal cancer.
I. Assess the objective overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
II. Estimate the duration of response, duration of stable disease (SD), progression free survival (PFS), and overall survival (OS).
III. Describe the safety of this regimen as determined by frequency and severity of associated adverse events.
I. Correlate the presence of colony stimulating factor 1 receptor (CSF1R)+ macrophages, regulatory T cells (Tregs), TILs (tumor infiltrating lymphocytes) and tumor PD-L1, CTLA-4 and PD1 expression (at baseline and post treatment) on tumor biopsies with response rate.
II. Characterize the systemic immune alteration through evaluation of mandatory pre and post cycle 1, and cycle 2, and at progression blood draws.
OUTLINE: This is a dose-escalation study of regorafenib.
Patients receive regorafenib orally (PO) once daily (QD) on days 1-21, nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W), and ipilimumab IV over 30 minutes every 6 weeks (Q6W). Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Clinical Trial of Regorafenib, Nivolumab, and Ipilimumab in Advanced Chemotherapy Resistant Metastatic MSS Colorectal Cancer|
|Estimated Study Start Date :||July 1, 2020|
|Estimated Primary Completion Date :||March 11, 2021|
|Estimated Study Completion Date :||March 11, 2021|
Experimental: Treatment (regorafenib, nivolumab, ipilimumab)
Patients receive regorafenib PO QD on days 1-21, nivolumab IV over 30 minutes Q2W, and ipilimumab IV over 30 minutes Q6W. Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity.
- Recommended dose level of the combination [ Time Frame: Up to 90 days post treatment ]Toxicities will be graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0. Dose limiting toxicity (DLT) will be graded per CTCAE v5.0. Any of the following adverse events occurring during the primary DLT observation period (4 weeks, from the time of first administration of regorafenib, ipilimumab and nivolumab[cycle 1 day 1] until the planned administration of the second cycle of regorafenib (cycle 2 day 1) that are at least probable attributable to many of the 3 agents or their combination will be classified as a DLT.
- Progression-free survival [ Time Frame: Time to disease progression/ relapse or death as a result of any cause, assessed up to 5 years ]Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Will be summarized using the Kaplan-Meier method.
- Duration of response [ Time Frame: Time to progression or death, assessed up to 5 years ]Assessed using RECIST v 1.1. Duration of response (possibly censored) will be reported for each response.
- Overall survival [ Time Frame: Time to death as a result of any cause, assessed up to 5 years ]Assessed using RECIST v 1.1. Will be summarized using the Kaplan-Meier method.
- Objective response rate (ORR) [ Time Frame: Up to 5 years post treatment ]ORR is defined as the percentage of measurable disease participants who have achieved either complete response (CR) or partial response (PR). Assessed using RECIST v 1.1.
- Immune response [ Time Frame: Baseline, assessed up to 5 years post treatment ]Correlative studies using serial tumor tissue and blood samples will assess immune response at pre-treatment and post-treatment. Will be summarized using exploratory methods. Changes in tumor and blood measurements from pre-treatment to post-treatment will be displayed graphically and summarized with responding individuals identified. Academic standard statistical methods will be used for these exploratory analyses.
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): NCT04362839
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Marwan G. Fakih 626-256-4673 ext 83087 email@example.com|
|Principal Investigator: Marwan G. Fakih|
|Principal Investigator:||Marwan G Fakih||City of Hope Medical Center|