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Colorectal CancerPhase 1NCT04868773

Study of Cabozantinib Plus TAS102 in mCRC as Salvage Therapy

A Phase 1 study testing Cabozantinib and TAS-102 in people with Colorectal Cancer and Colorectal Carcinoma, run by University of California, Irvine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Cabozantinib and TAS-102
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
16 Jul 2021to 9 Apr 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 1. 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.

Who cannot join

  • 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.
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  • 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).
  • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.5 x the laboratory ULN within 7 days before the first dose of study treatment.
  • Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Prior treatment with cabozantinib
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, subjects with a history of additional risk factors for torsades de pointes (e.g., long QT syndrome) are also excluded. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Corrected QT (QTc) = QT / ∛RR QT: duration of QT interval RR: duration of RR interval
  • History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
  • Inability to comply with study and follow-up procedures as judged by the Investigator
  • Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Has received a live vaccine within 30 days prior to the first dose of study intervention.
  • Has severe hypersensitivity (Grade ≥ 3) to TAS-102 or cabozantinib and/or any of their excipients.
  • Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Pregnant or lactating females.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Chao Family Comprehensive Cancer Center, University of California, Irvine

    Orange, California, 92868

Other trials in United States

About this study

Official title: A Phase 1 Study of the Combination of Cabozantinib With Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Adenocarcinoma (mCRC)

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).

Read the detailed description

Patients with histologically proven colorectal adenocarcinoma not amenable to curative treatment will be eligible to participate for this study. After meeting the eligibility criteria, patients will be given a IP regimen consisting of cabozantinib 20 - 40 mg given orally everyday for 28 days, trifluridine/tipiracil (TAS102) 25 - 35 mg/m2 on Days 1 - 5 and Days 8 - 12 every 28 days, and peg-filgrastim 6 mg subcutaneously on Day 13 every 28 days. Tumor assessments will be completed by CT/MRI every 8 weeks during the first year of treatment and every 3 months after the first year until patient comes off treatment.

Being tested
Cabozantinib, TAS-102
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called CABOMETYX®, COMETRIQ

    Oral cabozantinib

  • TAS-102Drug

    Also called trifluridine and tipiracil

    Oral TAS-102 (trifluridine and tipiracil)

Study groups in NCT04868773
Study groupRoleWhat they receive
Cabozantinib in Combination with TAS-102 (trifluridine/tipiracil)ExperimentalSubjects 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.
Receives: Drug: Cabozantinib; Drug: TAS-102

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (4)

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

    To evaluate the tolerability of administering cabozantinib in combination with TAS-102 in patients with metastatic colorectal cancer from the start of treatment, duration of treatment and up to 4 weeks after completion of study treatment. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.

    Measured: 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.

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

    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: 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.

  3. Overall Survival of Patients who Received Cabozantinib with TAS-102

    To evaluate overall survival in patients with metastatic colorectal cancer receiving cabozantinib in combination with TAS-102.

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

  4. Number of Participants with Objective Response Rate

    The ORR is determined by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) in patients with measurable disease, progression-free, safety regardless of grade and overall survival.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2021
  2. Study start16 Jul 2021
  3. Primary completion29 Aug 2023
  4. Study completion9 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This study is an open-label, single arm clinical trial.
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04868773
Sponsor's protocol ID
20216481
Other IDs
UCI 20-134
Status last verified
Apr 2026
First submitted
27 Apr 2021
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38103947

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cabozantinib and TAS-102 in people with Colorectal Cancer and Colorectal Carcinoma, run by University of California, Irvine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity [DLT] (time frame: From the start date of treatment until 4 weeks after the last patient has started treatment, an average of 1 year.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04868773, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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