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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if testing for tumor DNA in the blood can assist doctors in deciding whether regorafenib or TAS-102 is more effective for treating metastatic colorectal cancer. Both treatments work by targeting specific enzymes to slow or stop cancer cell growth. Individuals with advanced colorectal cancer who have not responded to at least two other treatments and can take either regorafenib or TAS-102 may be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that regorafenib is generally safe for people with metastatic colorectal cancer. Real-world studies have found that patients can tolerate the treatment, though some experience side effects. Common issues include fatigue and skin reactions on the hands and feet, while serious side effects are less common.

For trifluridine and tipiracil hydrochloride (TAS-102), studies have demonstrated that it helps patients with advanced colorectal cancer live longer compared to a placebo. Many patients report fatigue, but only a few experience severe side effects that require dose adjustments. Overall, both treatments are considered manageable, with most side effects being controllable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the potential of ctDNA testing to guide treatment decisions for colorectal cancer. Unlike the standard of care, which involves administering regorafenib or TAS-102 without genetic guidance, this trial uses ctDNA testing to tailor treatment to individual patients. ctDNA testing could provide a more personalized approach, potentially improving treatment outcomes by identifying those who might benefit most from a particular drug. By integrating ctDNA testing, researchers are hoping to refine treatment strategies and enhance the effectiveness of existing therapies.

What evidence suggests that ctDNA testing is effective for guiding treatment in advanced colorectal cancer?

Studies have shown that regorafenib can extend the lives of people with metastatic colorectal cancer when standard treatments fail. It achieves this by blocking proteins that promote cancer cell growth. Research also indicates that trifluridine and tipiracil can improve survival for patients with advanced colorectal cancer, particularly those who have exhausted other treatments. In this trial, one group of participants will receive either regorafenib or trifluridine and tipiracil with ctDNA testing, which tracks the cancer's response to treatment. The other group will receive these treatments according to standard care without ctDNA testing. Both treatments show promise, especially when combined with ctDNA testing. ^{2 6 7 8 9}

Who Is on the Research Team?

Kanwal P. Raghav

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22568966/

Regorafenib (BAY 73-4506) in advanced colorectal cancer Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7364795/

Efficacy and safety of regorafenib as beyond second-line ... The 5-year relative survival ranges from 90% for localized CRC to 14% for metastatic colorectal cancer (mCRC). The most common cause of death in patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01959269

Investigating the Use of Regorafenib (Stivarga®) in ... The purpose of the study is to investigate the safety and effectiveness of Stivarga in patients with metastatic colorectal carcinoma in routine use in Germany.

4. stivarga.com stivarga.com/mcrc/overall-survival

mCRC Efficacy Overall Survival - STIVARGA® (regorafenib) Survival, safety, and prognostic factors for outcome with regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/5/3/e007189

Regorafenib assessment in refractory advanced colorectal ... The RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11588636/

Efficacy and safety of regorafenib for the treatment of ... Our results confirm the safety of regorafenib as treatment of mCRC in real clinical practice. Although our population is less pretreated than in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3364125/

Regorafenib (BAY 73-4506) in advanced colorectal cancer Median progression-free survival was 107 days (95% CI, 66–161). At steady state, regorafenib and its active metabolites had similar systemic ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2012/203085Orig1s000CrossR.pdf

203085Orig1s000 - accessdata.fda.gov • Lack of exposure-response data from pivotal trial Bay 73-4506/14387,. • Lack of population pharmacokinetic analyses from Bay 73-4506/14387,.

9. cancernetwork.com cancernetwork.com/view/effectiveness-toxicity-and-survival-predictors-of-regorafenib-in-metastatic-colorectal-cancer-a-multicenter-study-of-routinely-collected-data

Effectiveness, Toxicity, and Survival Predictors of ... In conclusion, in our study of routinely collected data of 90 patients with mCRC, treatment with regorafenib was associated with OS outcomes ...