Study of Cabozantinib Plus TAS102 in mCRC as Salvage Therapy

NCT04868773 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 20216481UCI 20-134
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I clinical trial assessing the safety and recommended phase II dose of cabozantinib in combination with trifluridine/tipiracil (TAS102) in patients with metastatic colorectal carcinoma (mCRC).

Conditions

Colorectal Cancer; Colorectal Carcinoma; Metastatic Cancer; CRC

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity [DLT]

  To determine the Dose Limiting Toxicity (DLT) at Cycle 1 Day 28. A DLT is defined as the occurrence of specific toxicities within the DLT treatment period if judged by the Investigator to be possibly, probably, or definitely related to cabozantinib or TAS-102.

  From the start date of treatment until 4 weeks after the last patient has started treatment, an average of 1 year.

• Recommended Phase 2 Dose [RP2D]

  To determine the recommended Phase 2 Dose (RP2D) of cabozantinib in combination with TAS-102 in patients with metastatic colorectal carcinoma (mCRC) based on a 3+3 study design.

  From the start date of treatment until 4 weeks after the last patient has started treatment, an average of 1 year.

Secondary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

• Progression-Free Survival of Patients who Received Cabozantinib with TAS-102

  From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

• Overall Survival of Patients who Received Cabozantinib with TAS-102

  From date of registration for up to 18 months after last patient is enrolled or until death from any cause, whichever came first

• Number of Participants with Objective Response Rate

  From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

Study Arms (1)

Cabozantinib in Combination with TAS-102 (trifluridine/tipiracil)

EXPERIMENTAL

Subjects will receive cabozantinib in combination with TAS-102. Patients will receive cabozantinib on Days 1 - 28 and TAS-102 on Days 1-5 and Days 8-12, for a cycle length of 28 days.

Drug: Cabozantinib; Drug: TAS-102

Interventions

Cabozantinib DRUG

Oral cabozantinib

Also known as: CABOMETYX®, COMETRIQ

Cabozantinib in Combination with TAS-102 (trifluridine/tipiracil)

TAS-102 DRUG

Oral TAS-102 (trifluridine and tipiracil)

Also known as: trifluridine and tipiracil

Cabozantinib in Combination with TAS-102 (trifluridine/tipiracil)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed colorectal adenocarcinoma
• Must have locally advanced, recurrent, or metastatic disease not amenable to curative intent surgery or radiation.
• Must have progressed, or not tolerated, a fluoropyrimidine, irinotecan, oxaliplatin, and cetuximab or panitumumab (only for RAS wild-type). Prior exposure to bevacizumab or ramucirumab is allowed. Patients who have exhausted all other standard of care options are also eligible.
• Age ≥ 18 years
• Performance status: ECOG performance status ≤2 (Appendix A).
• Life expectancy of greater than 3 months
• Adequate organ and marrow function as defined below:
• leukocytes ≥ 3,000/mcL
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcl
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present
• creatinine \<1.5 ULN
• hemoglobin ≥ 8 g/dL
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg

You may not qualify if:

• Patients who have chemotherapy within 2 weeks prior to entering the study
• All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
• Patients may not be receiving any other investigational agents.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102, cabozantinib or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, the following conditions:
• ongoing or active infection
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.
• Other clinically significant disorders that would preclude safe study participation:
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• Active infection requiring systemic treatment (based on investigator assessment). Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection.

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

Related Publications (1)

• Dayyani F, Balangue J, Valerin J, Keating MJ, Zell JA, Taylor TH, Cho MT. A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma. Clin Colorectal Cancer. 2024 Mar;23(1):67-72. doi: 10.1016/j.clcc.2023.11.001. Epub 2023 Nov 27.

  PMID: 38103947 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

cabozantinib; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Farshid Dayyani, MD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Model Details: This study is an open-label, single arm clinical trial.

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 3, 2021
• Study Start: July 16, 2021
• Primary Completion: August 29, 2023
• Study Completion: April 9, 2024
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)