TAS-102 in ctDNA-defined Minimal Residual Disease in Colorectal Cancer After Completion of Adjuvant Chemotherapy

Study Overview
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Brief Summary
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To measure the level of circulating tumor DNA (ctDNA) in the blood of colorectal cancer patients after 6 months of receiving TAS-102 therapy. ctDNA is genetic material from tumor cells that can be found and measured in the blood.

Detailed Description
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Primary Objectives: The primary objective is to determine the 6-month ctDNA clearance rate in colorectal cancer patients with minimal residual disease following 6 months of TAS-102 therapy. Secondary Objectives: To determine the 3-month ctDNA clearance rate in colorectal cancer patients with minimal residual disease. To determine the disease free survival (DFS) amongst colorectal cancer patients with minimal residual disease following 6 months of TAS-102 therapy. To determine the overall survival (OS) amongst colorectal cancer patients with minimal residual disease following 6 months of TAS-102 therapy. To determine the safety and tolerability of TAS-102 for the treatment of colorectal cancer patients with minimal residual disease. Exploratory Objectives: To determine markers of response and resistance in archival tumor tissue including but not limited to immune profiles of tumor-infiltrating lymphocytes, expression of immune markers in tumor cells and microenvironment, and molecular markers (including but not limited to mutations, deletions, and/or amplifications or cancer molecular subtype) To determine changes in profiles of circulating lymphocytes and ctDNA with treatment To determine baseline characteristics in archival tumor and/or plasma that may predict clinical benefit

Official Title
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TAS-102 in ctDNA-defined Minimal Residual Disease in Colorectal Cancer After Completion of Adjuvant Chemotherapy

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histological confirmation of colorectal cancer Received post-R0 resection of stages II, III, or IV colorectal cancer and has completed of all planned adjuvant therapies Has no evidence of radiographic disease within 28 days (before or after) a positive ctDNA assay Has minimal residual disease as defined by positive ctDNA assay (completed as standard-of-care at MD Anderson) at least 3 months after completion of adjuvant chemotherapy. Patients may be identified for enrollment with any Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA assay for MRD. MRD status will be confirmed with the Signatera assay prior to initiation of therapy (unless the prior testing was also done with Signatera in which case this test would not require confirmation) Has adequate organ and marrow function as defined below: absolute neutrophil count: ≥1,000/mcL platelets: ≥100,000/mcL total bilirubin: ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥60 mL/min. Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation as follows: Clcr (mL/min) = [(140 - age) x (weight in kg) ÷ [72 x (serum creatinine in mg/dL)] [0.85 if female] Has ECOG performance status (PS) of 0 or 1 Is of age ≥ 18 years. Because no dosing or adverse-event data are currently available on the use of TAS-102 in patients, children <18 years of age are excluded from this study. Is able to understand and is willing to sign a written informed consent document. Is willing to utilize contraception. Female subjects agree to use highly effective contraception combined with an additional barrier method (eg, diaphragm, with a spermicide) while on study and for 7 months after last dose of study drug, and the same criteria are applicable to male subjects if they have a partner of childbirth potential. Male subject agrees to use a condom and not donate sperm while in this study and for 7 months after the last treatment. Exclusion Criteria: Has other concomitant active, invasive malignancies that may interfere with ctDNA analysis (known clonal hematopoesis of unknown potential allowed) Has serum electrolytes, potassium, calcium, or magnesium levels outside of the normal laboratory reference range which are clinically significant in the investigator's judgment Has significant concomitant health conditions including but not limited to severe autoimmune or cardiovascular disorders that may interfere with participation in the study Has a persistent adverse event, except alopecia and neuropathy, greater than or equal to grade 2 of the Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 Has another disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition that investigators suspect may (a) prohibit use of the investigational product, (b) affect interpretation of study results, or (c) put the patient at undue risk of harm Has known hypersensitivity to the trial drugs or their excipients or is at risk of allergic of anaphylactic reaction to drug product according to the Investigator's judgement Is pregnant or lactating Is unable to take medication orally or has any other condition that investigators believe may affect absorption of the investigational product Is receiving any other investigational agent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-102<br>TAS-102 should be taken by mouth 2 times a day, within 1 hour after your morning and evening meals (about 12 hours apart). | Drug: TAS-102<br>* GIven by PO<br>* Other names: Lonsurf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the 6-month ctDNA clearance rate in colorectal cancer patients with minimal residual disease following 6 months of TAS-102 therapy. |  | up to 6 months |