Study of ctDNA Guided Change in Tx for Refractory Minimal Residual Disease in Colon Adenocarcinomas

Proof of Concept Study of ctDNA Guided Change in Treatment for Refractory Minimal Residual Disease in Colon Adenocarcinomas

This is a phase 1b, prospective, single arm, non-randomized, open-label clinical trial determining the efficacy of adjuvant trifluridine and tipiracil (TAS-102) in combination with irinotecan in patients with ctDNA positive colon adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Colon Adenocarcinoma
• Intervention / Treatment: Drug: Irinotecan; Drug: TAS-102; Combination product: Standard Treatment; Diagnostic test: Signatera MRD ctDNA Assay

Detailed Description

Treatment on study will be administered in 14 day cycles.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chao Family Comprehensive Cancer Center University of California, Irvine; Phone Number: 1-877-827-7883; Email: ucstudy@uci.edu
• Study Contact Backup: Name: University of California Irvine Medical

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center, University of California, Irvine
      • Contact: Farshid Dayyani, MD, PhD; Phone Number: 877-827-8839; Email: ucstudy@uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed adenocarcinoma of the colon (high rectal cancer is eligible if resected and no radiation needed). Other histologies which are treated per NCCN guidelines for adjuvant colon cancer are eligible.
2. Must have Stage II, Stage III, or Stage IV colorectal cancer after curative intent resection eligible for adjuvant doublet chemotherapy for at least 3 months.
3. Must have ctDNA positive assay (tested by Signatera MRD assay) after at least 3 months of perioperative chemotherapy
4. Age ≥ 18 years
5. Performance status: ECOG performance status ≤2
6. Life expectancy of greater than 3 months

7. Adequate organ and marrow function as defined below:

   1. leukocytesL ≥ 3,000/mcL
   2. absolute neutrophil count: ≥ 1,500/mcL
   3. platelets: ≥ 80,000/mcl
   4. total bilirubin: within normal institutional limits
   5. AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present
   6. creatinine: <1.5 X ULN

8. The effects of TAS-102 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because topoisomerase inhibitors are known to be teratogenic, 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 90 days 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. 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).
9. Ability to swallow tablets
10. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

1. Patients who have had major surgery within 4 weeks, or chemotherapy or radiotherapy within 2 weeks prior to Cycle 1 Day 1
2. All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
3. Patients may not be receiving any other investigational agents.
4. Patients with known metastases.
5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102, irinotecan or other agents used in study.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Prior treatment with TAS-102 at any time or irinotecan within 90 days from enrollment.
8. 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.
9. Inability to comply with study and follow-up procedures as judged by the Investigator
10. Patients who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TASIRI; Patients randomized to the experimental arm ("TASIRI") will be treated with TAS-102 25mg/m2 p.o. on days 1-5 and irinotecan 180mg/m2 i.v. on day 1 every 14 days. If ANC <1500/uL on day 1 of a cycle, then G-CSF will be added on day 6 for three days.

Drug: Irinotecan; Given IV; Other Names: CPT-11; CAMPTOSAR; Drug: TAS-102; Given PO; Other Names: LONSURF; trifluoridine and tipiracil; Combination product: Standard Treatment; 6 cycles for a 2-week regimen (infusional 5FU based) and up to 4 cycles for a 3-week regimen (oral capecitabine based) after randomization; Diagnostic test: Signatera MRD ctDNA Assay; To be performed within 6-8 weeks of Cycle 1 Day 1. A Mid-treatment ctDNA is to be completed within 6 - 8 weeks of starting treatment. ctDNA is to also be completed within four weeks after completion of study treatment (+/- two weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of ctDNA positivity in treatment cohort after 6 cycles or at least 3 months of adjuvant treatment	Percent of patients positive for ctDNA after 6 cycles or at least 3 months months after starting adjuvant treatment will be used to estimate the efficacy of adjuvant trifluridine and tipiracil (TAS102) in combination with irinotecan in patients with ctDNA positive colon adenocarcinoma. The Signatera MRD ctDNA Assay will be used to measure ctDNA positivity.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Grade 3-5 Adverse Events	To evaluate the tolerability of drug-related grade 3-5 adverse events in patients with ctDNA positive colon adenocarcinoma. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.	8 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: Natera, Inc.; Taiho Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Farshid Dayyani, MD, PhD, Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Estimated): January 21, 2027
• Study Completion (Estimated): January 21, 2028

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Colonic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Deoxyribonucleosides; Thymidine; Irinotecan; Trifluridine; trifluridine tipiracil drug combination; tipiracil
• Other Study ID Numbers: 20206152; UCI 20-43 (Other Identifier: UCI Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No