Study of Cabozantinib Plus TAS102 in mCRC as Salvage Therapy

Completed · Phase 1

Conditions studied: Colorectal Cancer, Colorectal Carcinoma, Metastatic Cancer, CRC

In brief

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).

Key facts

Study ID

NCT04868773

Run by

University of California, Irvine

People needed

15

Starts

2021-07-16

Expected to finish

2024-04-09

Last updated by the study team

2026-04-24

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

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
• (PT)/INR or partial thromboplastin time (PTT) test < 1.3 x ULN
• The effects of cabozantinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to swallow tablets
• Ability to understand and the willingness to sign a written informed consent.

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
• Cardiovascular disorders: Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias; uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment; Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #3.2.8) for at least 1 week before first dose of study treatment.
• 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.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Serious non-healing wound/ulcer/bone fracture
• Malabsorption syndrome
• Uncompensated/symptomatic hypothyroidism
• Moderate to severe hepatic impairment (Child-Pugh B or C)
• Requirement for hemodialysis or peritoneal dialysis
• History of solid organ or allogenic stem cell transplant
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).

Where it is running

• Chao Family Comprehensive Cancer Center, University of California, Irvine — Orange, California, United States

Full record on ClinicalTrials.gov

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