Neoplasms

All Conditions

Digestive System Diseases

Adenocarcinoma

Colorectal Neoplasms

Rectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Cabozantinib

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.

Alexis Leal, MD

Data from a prior phase II study of single agent cabozantinib in metastatic, refractory colorectal cancer (NCT03542877) combined with the compelling preclinical data in colorectal mouse models utilizing cabozantinib combined with nivolumab have led to this concept for a clinical trial to combine cabozantinib and nivolumab in patients with metastatic MSS CRC in the third line setting and beyond.

This is an open-label, single-arm, 2-stage, phase II study of cabozantinib in combination with nivolumab in patients with refractory metastatic CRC. Up to 46 evaluable patients will be treated with cabozantinib 40 mg orally daily in combination with nivolumab 480 mg IV every 28 days. One cycle is defined as 28 days.

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.

Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer

A Phase II Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer

De-identified IPD will be available to other researchers for the purposes of investigating the research objectives of this clinical trial.

De-identified patient samples will be collected, processed and analyzed by our research laboratory collaborators to investigate our experimental objectives and endpoints outlined in the protocol. Research samples will be banked and additional testing/experiments may be undertaken pending the acquisition of additional funding to support this work.

De-identified IPD will be shared with study Sponsors (Bristol Myers Squibb and Exelixis) as well as collaborating CRO (Criterium doing business as AGICC (Academic GI Cancer Consortium)) during regular study teleconferences.

Future plans for sharing of IPD from final trial results have not yet been determined

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.

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).

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.

OS will be defined as the time from administration of the initial dose of study treatment until death from any cause.

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 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 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.

National Cancer Institute (NCI)

Criterium, Inc.

Bristol-Myers Squibb

Exelixis

University of Colorado, Denver

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

all subjects will recieve open label Cabozantinib 60 mg orally once daily

Cabometyx

Giuseppe Procopio, MD

This is an open label single arm, multicenter, phase II study designet To assess the progression free survival (PFS) of cabozantinib in patients pretreated with one immunocheckpoint inhibitor (CPI) in monotherapy or in combination

A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma

A Phase 2 Open Label Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma Pretreated With One immunochecKPOint INhibiTor (Anti PD1/PDL1): the BREAKPOINT Trial

To assess the progression free survival (PFS) of cabozantinib in patients pretreated with one immunocheckpoint inhibitor (CPI) in monotherapy or in combination

the efficacy based on objective response rates (ORR) according to RECIST 1:1 criteria

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Pembrolizumab

Lenvatinib

Avelumab

Axitinib

Ipilimumab

the subject who failed one prior line by nivolumab and ipilimumab

the subject who failed one prior line by PD-1/PD-L1 inhibitors in combination with VEGF TKI

the subject who failed the second line by immunotherapy (PD-1 antibody or PD-L1 antibody) following the first line VEGFR TKI

Cabometyx 60mg once daily, oral , up to Progression disease

This study is a phase 2, multicenter, interventional for cohort 1 \& 2, non-interventional for cohort 3, open-label trial of cabozantinib, with ORR as the primary efficacy endpoint. In total, 201 eligible subjects will enroll from 5 sites in Korea. The intervention for this cohort 1\&2 is only IMP, Cabometyx provided by Ipsen (off-label). Also, cohort 3 is just RWD without IMP (on-label)

Cohort 1 (post nivolumab and ipilimumab combination): the subject who failed one prior line by nivolumab and ipilimumab Cohort 2 (post pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, or avelumab and axitinib): the subject who failed one prior line by PD-1/PD-L1 inhibitors in combination with VEGF TKI Cohort 3 (post sequential immunotherapy after VEGFR TKI): the subject who failed the second line by immunotherapy (PD-1 antibody or PD-L1 antibody) following the first line VEGFR TKI Subjects will receive study treatment as long as they continue to experience a clinical benefit in the investigator's opinion or until there is unacceptable toxicity or the need for subsequent systemic anticancer therapy. Treatment may continue after radiographic progression per RECIST 1.1 as long as the investigator believes that the subject is still receiving clinical benefit from study treatment and that the potential benefit of continuing study treatment outweighs potential risks.

Cabozantinib as Subsequent Therapy to an Immune Checkpoint Based Therapy in Renal Cell Carcinoma

Cabozantinib as Subsequent Therapy to an Immune Checkpoint Based Therapy in Renal Cell Carcinoma, Phase 2, Interventional Study

Objective response rate , per RECIST 1.1, per investigator assessment

Time to response, per RECIST 1.1, per investigator assessment

Duration of response, per RECIST 1.1, per investigator assessment

Progression-free survival , per RECIST 1.1, per investigator assessment

Adverse Event, Serious adverse event by CTCAE 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer	NCT04963283	Colorectal Aden... Colon Cancer Colon Adenocarc... Rectum Cancer Rectal Cancer Rectal Adenocar... Colorectal Canc...	Cabozantinib Nivolumab	18 Years -	University of Colorado, Denver
A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma	NCT03463681	Metastatic Rena...	Cabometyx	18 Years - 85 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma	NCT03463681	Metastatic Rena...	Cabometyx	18 Years - 85 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Cabozantinib as Subsequent Therapy to an Immune Checkpoint Based Therapy in Renal Cell Carcinoma	NCT04714697	Renal Cell Canc...	Cabometyx	19 Years -	Asan Medical Center
A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma	NCT03463681	Metastatic Rena...	Cabometyx	18 Years - 85 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for cabometyx

Every month we try and update this database with for cabometyx cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cabometyx

Every month we try and update this database with for cabometyx cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cabometyx cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.