ctDNA Testing for Colon Cancer Treatment Prediction

Recruiting at 1029 trial locations

Overseen By Chaoyuan Kuang

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

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

635 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II/III trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) testing in the blood works in predicting treatment for patients with stage IIA colon cancer after surgery. ctDNA are circulating tumor cells that are shed by tumors into the blood. Finding ctDNA in the blood means that there is very likely some small amounts of cancer that remain after surgery. However, this cancer, if detected, cannot be found on other tests usually used to find cancer, as it is too small. Testing for ctDNA levels may help identify patients with colon cancer after surgery who do benefit, and those who do not benefit, from receiving chemotherapy.

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.

What data supports the effectiveness of the drug Capecitabine (Xeloda) for colon cancer treatment?

Research shows that Capecitabine (Xeloda) is as effective as the standard treatment of 5-FU and leucovorin for colorectal cancer, with similar survival rates and less toxicity. It is also effective when combined with oxaliplatin, providing a well-tolerated treatment option with good response rates. ^{1 2 3 4 5}

Is ctDNA testing for colon cancer treatment prediction safe for humans?

Capecitabine (Xeloda), an oral form of chemotherapy, has been shown to be generally safe in humans, with studies indicating it causes fewer side effects like diarrhea and nausea compared to traditional intravenous chemotherapy. However, it may cause hand-foot syndrome (redness and swelling of the hands and feet) and increased bilirubin levels (a substance in the blood that can indicate liver issues). ^{1 2 3 5 6}

What makes the drug capecitabine unique for colon cancer treatment?

Capecitabine is unique because it is an oral drug that is designed to be activated directly at the tumor site, mimicking continuous infusion of 5-FU but with less toxicity and more convenience compared to traditional intravenous administration. ^{1 3 5 7 8}

Research Team

Van K Morris

Principal Investigator

NRG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

Xeloda in colorectal cancer. [2015]

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

Current status of capecitabine in the treatment of colorectal cancer. [2018]

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

Role of oral chemotherapy in colorectal cancer. [2015]

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

XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. [2022]

5. United States 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. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Capecitabine--a review of its antitumor activity and toxicity in clinical studies]. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Capecitabine as first-line treatment in colorectal cancer. Pooled data from two large, phase III trials. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. [2017]