ctDNA Testing for Colorectal Cancer

Overseen By Kanwal Raghav

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Heart failure, Angina, Brain tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle, up to 18 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with your doctor to understand how your current treatments might interact with the trial medications regorafenib or TAS-102.

What data supports the effectiveness of the drug Regorafenib and Trifluridine/Tipiracil Hydrochloride for colorectal cancer?

Research shows that using both Regorafenib and Trifluridine/Tipiracil together can significantly increase survival time in patients with metastatic colorectal cancer compared to using either drug alone. ^{1 2 3 4 5}

What safety data exists for Regorafenib and Trifluridine/Tipiracil in humans?

Regorafenib and Trifluridine/Tipiracil are FDA-approved for treating metastatic colorectal cancer, indicating they have been evaluated for safety in humans. However, Regorafenib can be difficult to use in patients with other health issues like blood clots, bleeding, or heart problems. ^{1 2 3 6 7}

How is the drug combination of Regorafenib, Trifluridine, and Tipiracil unique for treating colorectal cancer?

This drug combination is unique because it is used for patients with metastatic colorectal cancer who no longer respond to standard chemotherapy. Regorafenib is a multitargeted tyrosine kinase inhibitor that can lead to durable responses, while Trifluridine/Tipiracil is a cytotoxic combination that has shown significant improvements in overall survival. They are used as third-line treatments and differ in their side effects, with Regorafenib causing skin reactions and fatigue, and Trifluridine/Tipiracil causing myelosuppression (a decrease in bone marrow activity). ^{1 2 3 6 8}

Research Team

Kanwal P. Raghav

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic colorectal cancer who have tried at least two prior treatments, including specific chemotherapy drugs. They must be able to take oral medications, complete questionnaires, and provide blood samples. Pregnant women are excluded, as well as those with severe infections, recent heart issues, kidney failure requiring dialysis, or symptomatic brain tumors.

Inclusion Criteria

I can understand and sign the consent form.

Patients must have ability to complete questionnaire(s) by themselves or with assistance.

Patients must be willing to provide blood samples for correlative studies.

Exclusion Criteria

I have not had serious heart issues like severe heart failure or a recent heart attack.

I do not have a serious ongoing infection.

I have brain or meningeal tumors but have been stable for over 3 months after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive regorafenib or TAS-102 based on ctDNA testing results or standard of care. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 2 weeks and then monthly.

Up to 18 months

1 visit at 2 weeks, then monthly visits

Treatment Details

Interventions

• Regorafenib
• Trifluridine and Tipiracil Hydrochloride

Trial Overview The study is testing if using circulating cell-free tumor DNA (ctDNA) can guide treatment between regorafenib and TAS-102 effectively in patients whose colorectal cancer has spread. Both drugs aim to block enzymes that promote tumor cell growth.

Participant Groups

Group I: Arm I (ctDNA testing, regorafenib, TAS-102) Experimental Treatment 5 Interventions

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.

Group II: Arm II (SOC) Active Control 5 Interventions

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.

Regorafenib is already approved in United States, European Union for the following indications:

Approved in United States as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Approved in European Union as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

TK-1, TP, Ang-2, and Tie-2 mRNA expression in plasma-derived microvesicles of chemo-refractory metastatic colorectal cancer patients. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Early modulation of Angiopoietin-2 plasma levels predicts benefit from regorafenib in patients with metastatic colorectal cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

An Observational Study of Trifluridine/Tipiracil-Containing Regimen Versus Regorafenib-Containing Regimen in Patients With Metastatic Colorectal Cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Survival Benefit of Crossover Administration of Regorafenib and Trifluridine/Tipiracil Hydrochloride for Patients With Metastatic Colorectal Cancer: Exploratory Analysis of a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study (REGOTAS). [2021]

5. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Clinical Outcomes Following Trifluridine/Tipiracil Treatment for Patients With Metastatic Colorectal Cancer Ineligible for Regorafenib Treatment. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Current Options for Third-Line Treatment of Metastatic Colorectal Cancer. [2022]