Circulating Cell-Free Tumor DNA Testing in Guiding Treatment for Patients With Advanced or Metastatic Colorectal Cancer

NCT03844620 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2018-0233NCI-2019-00246
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies circulating cell-free tumor DNA testing to guide treatment with regorafenib or TAS-102 in patients with colorectal cancer that has spread to other areas of the body. Studying samples of blood from patients with colorectal cancer may help doctors understand how well patients respond to treatment. Regorafenib and TAS-102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known how well ctDNA testing works in guiding treatment with regorafenib and TAS-102 for patients with advanced or metastatic colorectal cancer.

Conditions

Refractory Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Early change in circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) as a predictor of radiographic progression (Arm II-SOC)

  Number of patients with rise in ctDNA level will be compared to Number of patients with progression of disease on scans.

  First 4 months after treatment initiation

• Treatment-related adverse events (TRAEs) of interest (grade 3/4 toxicity, intolerable grade 2 toxicity, or any toxicity requiring dose reduction) between arms

  Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. To compare the proportions of patients who have experienced TRAEs of interest within the first 4 months between the two treatment arms, Fisher's exact test will be used.

  First 4 months after treatment initiation

Secondary Outcomes (10)

• Mean patient-reported outcomes (PROs) score as per MD Anderson Symptom Inventory (MDASI-GI)

  Up to 18 months

• Mean patient-reported outcomes (PROs) score as per PRO-CTCAE

  Up to 18 months

• Percentage of patients with partial response (PR)

  Up to 18 months

• Percentage of patients with stable disease (SD)

  Up to 18 months

• Overall survival (OS)

  Up to 18 months

Study Arms (2)

Arm I (ctDNA testing, regorafenib, TAS-102)

EXPERIMENTAL

Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle. Patients in this arm will get ctDNA testing and will continue treatment beyond 1st cycle depending on ctDNA results. Beyond that patients will continue treatment in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Procedure; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Regorafenib; Drug: Trifluridine and Tipiracil Hydrochloride

Arm II (SOC)

ACTIVE COMPARATOR

Patients will receive either regorafenib by mouth on days 1-21 every 28 day cycle or TAS-102 by mouth twice daily on days 1-5 and 8-12 every 28 day cycle as per standard of care. Patients in this arm will continue treatment in the absence of disease progression or unacceptable toxicity.

Other: Best Practice; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Regorafenib; Drug: Trifluridine and Tipiracil Hydrochloride

Interventions

Best Practice OTHER

Receive SOC

Also known as: standard of care, standard therapy

Arm II (SOC)

Laboratory Procedure OTHER

Undergo ctDNA testing

Also known as: Lab Test, Lab Tests, Laboratory Test, Test, Tests

Arm I (ctDNA testing, regorafenib, TAS-102)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (ctDNA testing, regorafenib, TAS-102); Arm II (SOC)

Questionnaire Administration OTHER

Ancillary studies

Arm I (ctDNA testing, regorafenib, TAS-102); Arm II (SOC)

Regorafenib DRUG

Given by mouth

Also known as: BAY 73-4506, Stivarga

Arm I (ctDNA testing, regorafenib, TAS-102); Arm II (SOC)

Trifluridine and Tipiracil Hydrochloride DRUG

Given by mouth

Also known as: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

Arm I (ctDNA testing, regorafenib, TAS-102); Arm II (SOC)

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 colorectal cancer.
• Patients must have advanced or metastatic disease with no curative options.
• Patients must have radiographically evaluable disease.
• Patients must have had at least 2 prior therapies for mCRC (including fluorouracil \[5-FU\], oxaliplatin, irinotecan, bevacizumab; cetuximab/panitumumab \[for RAS wild type (WT) patients\]) and have either progressed on or intolerant to these agents or use of these agents is contraindicated.
• Patients must be clinically eligible for either regorafenib or TAS-102 as per their treating physician.
• Patients must have a negative serum pregnancy test done less than are equal to 14 days prior to randomization for women of childbearing potential only. 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.
• Patients must have ability to complete questionnaire(s) by themselves or with assistance.
• Patients must have ability to provide informed written consent.
• Patients must be willing to return to enrolling institution for follow-up as per study schedule.
• Patients must be willing to provide blood samples for correlative studies.
• Any of the following: Pregnant or nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

You may not qualify if:

• Patient who have received prior TAS-102 are eligible to enroll on the study if they can receive regorafenib and vice-versa. Otherwise these patients will be excluded from the study.
• Congestive heart failure \> New York Heart Association (NYHA) class 2, unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 3 months prior to randomization.
• Ongoing infection \> grade 2 CTCAE version 4.0.
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 3 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to brain lesions at the time of randomization (Note: patient must not be undergoing acute steroid therapy or taper \[chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies\]).
• Renal failure requiring hematological or peritoneal dialysis.
• Patients unable to swallow oral medications.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Practice Guidelines as Topic; Standard of Care; Clinical Laboratory Techniques; regorafenib; Trifluridine; trifluridine tipiracil drug combination

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)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kanwal Raghav

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 18, 2019
• Study Start: January 29, 2019
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)