A Phase II Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT04963283|
Recruitment Status : Recruiting
First Posted : July 15, 2021
Last Update Posted : July 15, 2021
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Adenocarcinoma Colon Cancer Colon Adenocarcinoma Rectum Cancer Rectal Cancer Rectal Adenocarcinoma Colorectal Cancer||Drug: Cabozantinib Drug: Nivolumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a Phase 2, single-arm, open-label study of cabozantinib in combination with nivolumab in subjects with metastatic CRC refractory to standard of care options. The primary endpoint is DCR at 16 weeks. A Simon 2-stage optimal design will be used.|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer|
|Actual Study Start Date :||June 23, 2021|
|Estimated Primary Completion Date :||February 9, 2024|
|Estimated Study Completion Date :||February 9, 2025|
Experimental: Cabozantinib 40 mg orally daily in combination with nivolumab 480 mg IV every 28 days.
Cabozantinib is supplied as 20-mg tablets and will be administered orally at a dose of 40 mg/day.
Nivolumab is supplied in 100 mg/Vial (10 mg/mL) vials and will be administered IV at a dose of 480 mg every 28 days.
Cabozantinib is a multi-targeted inhibitor of RTKs. The targets of cabozantinib include several RTKs known to play important roles in tumor cell proliferation and/or tumor neovascularization, namely MET, VEGFR2 (also known as KDR), AXL, and RET. Other recognized targets of cabozantinib include ROS1, TRKA, TRKB, TIE2, TYRO3, and MER, two additional members of the VEGFR family (VEGFR1, VEGFR3), and the closely related RTKs KIT and FLT-3. The mode of action for cabozantinib is similar to other drugs targeting RTKs: binding in a fully reversible manner to a region of the kinase domain (including the ATP-binding site) which forces the kinase activation loop into a pseudo-inactive conformation, thereby inhibiting subsequent catalytic activity.
Other Name: Cabometyx
Nivolumab is a human monoclonal antibody that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. Nivolumab binds specifically to the human PD-1 receptor and inhibits the interaction of PD-1 with its ligands, programmed death ligands-1 (PD-L1) and 2 (PD-L2), which promotes immune responses and antigen-specific T-cell responses to foreign- and self- antigens. Nivolumab is expressed in Chinese hamster ovary (CHO) cells and is produced using standard mammalian cell cultivation and chromatographic purification technologies.
Other Name: Opdivo
- Disease Control Rate (DCR) [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]DCR is defined using the RECIST 1.1 criteria as the proportion of subjects who have achieved confirmed complete response (CR), confirmed partial response (PR) or stable disease (SD) at 16-weeks.
- Objective Response Rate (ORR) [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]ORR is defined using the RECIST 1.1 criteria as the proportion of subjects with a confirmed complete response (CR) or confirmed partial response (PR).
- Progression Free Survival (PFS) [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]PFS will be defined as the time from administration of the initial dose of study treatment to evidence of radiographic progression as defined by RECIST 1.1 criteria or death from any cause without evidence of disease progression, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]OS will be defined as the time from administration of the initial dose of study treatment until death from any cause.
- Safety and Tolerability [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Safety and tolerability analysis of cabozantinib in combination with nivolumab summarized by dose and severity as assessed by the CTCAE version 5.0 and relationship to study drugs.
- Exploratory Biomarker analysis - Whole Blood [ Time Frame: Study start date to study end date, up to 24 months ]Exploratory analysis of predictive and pharmacodynamic markers by obtaining pre- and on-treatment whole blood samples pretreatment and +/- 5 days of Cycle 2 Day 1 of treatment for each patient and archived for future studies and analysis.
- Exploratory Biomarker analysis - Tumor tissue [ Time Frame: Study start date to study end date, up to 24 months ]Exploratory analysis of predictive and pharmacodynamic markers by obtaining pre- and on-treatment tumor biopsies pre-treatment and +/- 5 days of Cycle 2 day 1 of treatment for a cohort of 20 patients for VECTRA analysis to evaluate for immune cell infiltration. Tissue will be archived for future studies.
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): NCT04963283
|Contact: Matt Lee||(720)848-0630||Matthew.R.Lee@cuanschutz.edu|
|Contact: Mike Wacker||(720)848-3427||Michael.Wacker@cuanschutz.edu|
|United States, Colorado|
|University of Colorado Hospital||Recruiting|
|Aurora, Colorado, United States, 80012|
|Contact: Matt Lee 720-848-0630 Matthew.R.Lee@cuanschutz.edu|
|Principal Investigator: Alexis Leal, MD|
|UCHealth Memorial Hospital Central||Recruiting|
|Colorado Springs, Colorado, United States, 80909|
|Contact: Alicia Deschaine 719-365-6855 firstname.lastname@example.org|
|Principal Investigator: Robert Hoyer|
|UCHealth Harmony Campus||Recruiting|
|Fort Collins, Colorado, United States, 80528|
|Contact: Nathan Ketelhut 970-297-6150 email@example.com|
|Principal Investigator: Steven Schuster|
|UCHealth Family Medicine - Greeley||Recruiting|
|Greeley, Colorado, United States, 80634|
|UCHealth Medical Center of the Rockies||Recruiting|
|Loveland, Colorado, United States, 80538|
|Principal Investigator:||Alexis Leal, MD||University of Colorado, Denver|