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

NCT04920032 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 20206152UCI 20-43
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colon Adenocarcinoma; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percentage of Grade 3-5 Adverse Events

  8 weeks

Study Arms (1)

TASIRI

EXPERIMENTAL

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: TAS-102; Drug: Irinotecan; Combination Product: Standard Treatment; Diagnostic Test: Signatera MRD ctDNA Assay

Interventions

TAS-102 DRUG

Given PO

Also known as: LONSURF, trifluoridine and tipiracil

TASIRI

Irinotecan DRUG

Given IV

Also known as: CAMPTOSAR, CPT-11

TASIRI

Standard Treatment COMBINATION_PRODUCT

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

TASIRI

Signatera MRD ctDNA Assay DIAGNOSTIC_TEST

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)

TASIRI

Eligibility Criteria

• Age: 18 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 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.
• 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.
• Must have ctDNA positive assay (tested by Signatera MRD assay) after at least 3 months of perioperative chemotherapy
• Age ≥ 18 years
• Performance status: ECOG performance status ≤2
• Life expectancy of greater than 3 months
• Adequate organ and marrow function as defined below:
• leukocytesL ≥ 3,000/mcL
• absolute neutrophil count: ≥ 1,500/mcL
• platelets: ≥ 80,000/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 X ULN
• 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:

You may not qualify if:

• Patients who have had major surgery within 4 weeks, or chemotherapy or radiotherapy within 2 weeks prior to Cycle 1 Day 1
• 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.
• Patients with known metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102, irinotecan or other agents used in study.
• 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.
• Prior treatment with TAS-102 at any time or irinotecan within 90 days from enrollment.
• 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
• Patients who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. -

Sponsors & Collaborators

• University of California, Irvine: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator
• Natera, Inc.: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Interventions

trifluridine tipiracil drug combination; Trifluridine; tipiracil; Irinotecan

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

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids

Study Officials

• Farshid Dayyani, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

CONTACT

1-877-827-7883; ucstudy@uci.edu

University of California Irvine Medical

CONTACT

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: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 9, 2021
• Study Start: August 26, 2021
• Primary Completion (Estimated): January 21, 2027
• Study Completion (Estimated): January 21, 2028
• Last Updated: April 13, 2026

Record last verified: 2025-04

Locations

US (1)