ctDNA Testing for Colon Cancer Treatment Prediction

Not currently recruiting at 1048 trial locations

Overseen By Chaoyuan Kuang

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

Must not be taking: Antineoplastic therapy

Disqualifiers: Metastatic disease, Organ transplant, 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: 14

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a blood test for ctDNA (tiny bits of tumor DNA in the blood) can guide the need for chemotherapy in people with stage IIA colon cancer after surgery. The trial includes two groups: one receives regular monitoring if no ctDNA is found, while the other receives chemotherapy options, such as Capecitabine (Xeloda), Fluorouracil (5-FU or Adrucil), Leucovorin Calcium (Folinic acid), and Oxaliplatin, if ctDNA is detected. The study seeks participants who have undergone surgery to remove stage IIA colon cancer and have been advised to pursue active monitoring rather than immediate chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on a coumarin-derivative anticoagulant, you must agree to weekly monitoring of your INR if you are randomized to Arm 2 and receive capecitabine.

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

Previous studies have used the drugs oxaliplatin, capecitabine, fluorouracil, and leucovorin to treat colon cancer. These studies show that the drugs are generally safe, though they can cause some side effects. Oxaliplatin may cause tingling or numbness in the hands and feet. Capecitabine might lead to fatigue or diarrhea. Fluorouracil is usually safe, but it can sometimes lower blood cell counts. Leucovorin is generally well-tolerated and enhances the effectiveness of fluorouracil. These treatments are commonly used for colon cancer, indicating their safety for many people. However, individual reactions can vary, so discussing possible side effects with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses ctDNA testing, which could revolutionize how we predict colon cancer treatment outcomes. Unlike traditional methods that rely solely on imaging or biopsy, ctDNA testing detects tiny fragments of cancer DNA in the blood. This could help identify patients who need aggressive treatment versus those who might avoid unnecessary chemotherapy. By tailoring treatments based on ctDNA results, doctors aim to improve patient outcomes and reduce side effects, making cancer care more personalized and precise.

What evidence suggests that this trial's treatments could be effective for colon cancer?

Studies have shown that combining oxaliplatin with capecitabine can benefit patients with colon cancer. This treatment plan has been linked to better survival rates and used in various therapies. In this trial, participants with detected ctDNA will receive this combination. Another combination, oxaliplatin with fluorouracil and leucovorin, has also yielded good results, particularly in advanced colon cancer, and serves as another option for participants with detected ctDNA. Research suggests these treatments can help eliminate leftover cancer cells after surgery. Additionally, testing for ctDNA (tiny pieces of cancer DNA in the blood) might identify those who will benefit most from these chemotherapy treatments. Overall, these combinations show promise in effectively managing colon cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Van K Morris

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with stage IIA colon cancer who've had surgery. They must have good blood counts, organ function, and a performance status of 0 or 1 (able to carry out daily activities). No other cancers in the last 5 years except certain non-aggressive types are allowed. Patients can't join if they've had recent chemotherapy or have serious heart issues, infections, neuropathy, DPD deficiency, pregnancy/lactation, or conditions that could interfere with the study.

Inclusion Criteria

Your ANC must be at least 1,200 cells per cubic millimetre of blood within four weeks prior to randomization.

My oncologist agrees I can be monitored without immediate chemotherapy.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Prior testing with any available ctDNA test as part of the management of colon cancer, is not permitted.

I haven't had cancer treatment, except hormone therapy, in the last 5 years.

My heart condition allows me to take the GI005 treatment drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy or undergo active surveillance based on ctDNA detection

6 months

Every 14-21 days for chemotherapy cycles

Follow-up

Participants are monitored for recurrence-free survival and overall survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Leucovorin
• Leucovorin Calcium
• Oxaliplatin

Trial Overview The trial is testing whether checking ctDNA levels in the blood after surgery can predict which stage IIA colon cancer patients might benefit from chemotherapy. It's comparing outcomes between those who receive chemo drugs like Leucovorin Calcium, Oxaliplatin, Capecitabine and Fluorouracil versus those under observation without these treatments.

How Is the Trial Designed?

Group I: Arm II (blood tested for ctDNA at baseline) Experimental Treatment 6 Interventions

Patients are assigned to 1 of 2 groups. GROUP I (ctDNA DETECTED): At the discretion of the investigator, patients receive either oxaliplatin IV over 2 hours on day 1, leucovorin IV over 2 hours on day 1, and fluorouracil IV bolus over 2-4 minutes on day 1 and then by continuous IV over 46-48 hours repeated every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 1-14 repeated every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity at the discretion of the investigator. GROUP II (ctDNA NOT DETECTED): Patients undergo active surveillance.

Group II: Arm I (blood stored and tested for ctDNA later) Active Control 1 Intervention

Patients undergo active surveillance.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

5-fluorouracil (5-FU) remains a key chemotherapy drug for colorectal cancer, but its oral form was previously abandoned due to inconsistent absorption; however, Xeloda (capecitabine) offers a solution by being an orally administered drug that is selectively activated in tumors, leading to higher local concentrations of 5-FU.

In phase II clinical trials for colorectal cancer, Xeloda demonstrated response rates of 21-24% and a median time to disease progression of 127-230 days, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. Brito, RA., Medgyesy, D., Zukowski, TH., et al.[2017]

Xeloda (capecitabine) is an oral pro-drug that is effectively converted to 5-fluorouracil in the body, particularly in colorectal cancer, where the enzyme needed for activation is more active.

In large phase III trials, capecitabine demonstrated at least equal efficacy to the standard intravenous treatment of 5-FU and leucovorin, with better response rates and significantly lower toxicity, suggesting it may become the preferred treatment for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xeloda in colorectal cancer. Cassidy, J.[2015]

Recent trials indicate that oral fluoropyrimidine agents like capecitabine (Xeloda) and UFT/leucovorin are as effective as standard intravenous 5-FU in treating advanced colorectal cancer, showing similar response rates and survival outcomes.

These oral agents also have the added benefit of reducing side effects such as neutropenia and stomatitis, making them a promising option for patients undergoing treatment for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oral chemotherapy in colorectal cancer. Donehower, RC.[2015]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

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