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

NCT ID: NCT04920032

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-26
• Study Completion Date: 2026-12-31

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.

Detailed Description

Treatment on study will be administered in 14 day cycles.

Conditions

Colon Adenocarcinoma; Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TAS-102

Intervention Type: DRUG

Given PO

Irinotecan

Intervention Type: DRUG

Given IV

Standard Treatment

Intervention Type: 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

Signatera MRD ctDNA Assay

Intervention Type: 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)

Interventions

TAS-102

Given PO

Intervention Type: DRUG

Irinotecan

Given IV

Intervention Type: DRUG

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

Intervention Type: COMBINATION_PRODUCT

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)

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

LONSURF; trifluoridine and tipiracil; CAMPTOSAR; CPT-11

Eligibility Criteria

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. -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Natera, Inc.

INDUSTRY

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Farshid Dayyani

Associate Clinical Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Farshid Dayyani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Locations

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

Role: CONTACT

ucstudy@uci.edu

1-877-827-7883

University of California Irvine Medical

Role: CONTACT

Facility Contacts

Farshid Dayyani, MD, PhD

Role: primary

ucstudy@uci.edu

877-827-8839

Other Identifiers

UCI 20-43

Identifier Type: OTHER

Identifier Source: secondary_id

20206152

Identifier Type: -

Identifier Source: org_study_id