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

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed adenocarcinoma of thecolon (high rectal cancer is eligible if resected and no radiation needed). Otherhistologies which are treated per NCCN guidelines for adjuvant colon cancer areeligible.

2. Must have Stage II, Stage III, or Stage IV colorectal cancer after curative intentresection eligible for adjuvant doublet chemotherapy for at least 3 months.

3. Must have ctDNA positive assay (tested by Signatera MRD assay) after at least 3months 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:

8. leukocytesL ≥ 3,000/mcL

9. absolute neutrophil count: ≥ 1,500/mcL

10. platelets: ≥ 80,000/mcl

11. total bilirubin: within normal institutional limits

12. AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X ifliver metastases are present

13. creatinine: <1.5 X ULN

14. The effects of TAS-102 on the developing human fetus at the recommended therapeuticdose are unknown. For this reason and because topoisomerase inhibitors are known tobe teratogenic, women of child-bearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry, for the duration of study participation, and for 90 days followingcompletion of therapy. Should a woman become pregnant or suspect she is pregnantwhile participating in this study, she should inform her treating physicianimmediately. a. A female of child-bearing potential is any woman (regardless of sexualorientation, having undergone a tubal ligation, or remaining celibate by choice) whomeets 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 radiotherapywithin 2 weeks prior to Cycle 1 Day 1

2. All toxicities attributed to prior anti-cancer therapy other than alopecia must haveresolved 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 orbiologic composition to TAS-102, irinotecan or other agents used in study.

6. Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

7. Prior treatment with TAS-102 at any time or irinotecan within 90 days fromenrollment.

8. History of another primary cancer within the last 3 years with the exception ofnon-melanoma skin cancer, early-stage prostate cancer, or curatively treatedcervical carcinoma in-situ.

9. Inability to comply with study and follow-up procedures as judged by theInvestigator

10. Patients who are pregnant or nursing due to the potential for congenitalabnormalities and the potential of this regimen to harm nursing infants. -