Using ctDNA to guide treatment changes for colon cancer

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

This study is testing if a new combination of cancer treatments can help people with colon cancer who still have traces of the disease after surgery feel better and live longer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, Irvine (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Orange, California)
• Trial ID: NCT04920032 on ClinicalTrials.gov

What this trial studies

This phase 1b clinical trial evaluates the effectiveness of combining adjuvant trifluridine and tipiracil (TAS-102) with irinotecan in patients with colon adenocarcinoma who test positive for circulating tumor DNA (ctDNA). The treatment will be administered in 14-day cycles, focusing on patients who have undergone curative intent resection and are eligible for adjuvant chemotherapy. The study aims to determine if ctDNA-guided therapy can improve outcomes for patients with minimal residual disease.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed colon adenocarcinoma who are ctDNA positive after prior chemotherapy.

Not a fit: Patients with non-adenocarcinoma histologies or those without detectable ctDNA may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective treatment strategies for patients with refractory colon adenocarcinoma.

How similar studies have performed: While the use of ctDNA in guiding treatment is a growing area of interest, this specific combination of therapies in colon adenocarcinoma is relatively novel and has not been extensively tested in prior studies.

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. -

Where this trial is running

Orange, California

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

Study contacts

• Principal investigator: Farshid Dayyani, MD, PhD — Chao Family Comprehensive Cancer Center
• Study coordinator: Chao Family Comprehensive Cancer Center University of California, Irvine

Conditions: Colon Adenocarcinoma, Colorectal Cancer