5-Fluorouracil for Colorectal Cancer

Overseen By Elahe Mollapour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inova Health Care Services

Must be taking: 5-FU

Disqualifiers: Untreated brain metastasis, DPD deficiency, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adjusting the dose of the chemotherapy drug 5-fluorouracil (5-FU) based on blood levels can more effectively treat metastatic colon cancer. It examines the use of 5-FU with other chemotherapy drugs such as leucovorin, oxaliplatin, and irinotecan, either alone or in combination. The trial targets individuals with confirmed metastatic colorectal cancer who have not yet received treatment. Participants must also have normal organ function and a life expectancy of more than three months. As a Phase 2 trial, the research focuses on evaluating 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that 5-fluorouracil (5-FU) is generally well-tolerated by those treated for colorectal cancer. Some studies indicate that combining 5-FU with other drugs like leucovorin and oxaliplatin can enhance treatment effectiveness. However, 5-FU can cause side effects. One study examined its effects on the heart, but serious heart problems remain rare.

Patients might experience nausea, diarrhea, or a drop in white blood cells, increasing infection risk. These side effects are often manageable with medical assistance.

This trial is in Phase 2, indicating that earlier studies have shown 5-FU to be relatively safe. This phase focuses on its effectiveness and dose adjustment. The FDA has approved 5-FU for treating other cancers, suggesting a good safety record.

Prospective participants should consult their doctors to understand both potential benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using 5-fluorouracil (5-FU) for colorectal cancer because it allows for personalized treatment adjustments based on real-time plasma levels. Unlike traditional chemotherapy regimens that follow a fixed dosing schedule, this approach tailors 5-FU doses to individual patients, potentially improving effectiveness and minimizing side effects. By combining 5-FU with other drugs like leucovorin, oxaliplatin, and irinotecan, this method could enhance the overall impact on cancer cells, offering a more targeted treatment option compared to existing standards.

What evidence suggests that adjusting the dose of 5-fluorouracil could be an effective treatment for metastatic colon cancer?

Research shows that 5-Fluorouracil (5-FU) plays a crucial role in chemotherapy for colorectal cancer. Studies have demonstrated that it extends patient survival and lowers the risk of cancer recurrence. In this trial, participants will receive 5-FU combined with other drugs, such as oxaliplatin or irinotecan, or both, to boost its effectiveness. Some research suggests that adjusting the dose based on blood levels might further enhance its effectiveness. However, cancer may still return after treatment. Overall, 5-FU remains a strong option for treating colorectal cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Jasmine Huynh

Principal Investigator

Inova Schar Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic colorectal cancer. Participants should be suitable for chemotherapy and have not been treated with the study drugs before. Specific details about inclusion and exclusion criteria are not provided, but typically these would relate to overall health status, prior treatments, and other medical conditions.

Inclusion Criteria

Life expectancy > 3 months

I can take care of myself but might not be able to do heavy physical work.

I haven't had treatment for cancer that has spread, but if I had 5-FU or FOLFOX, it was over 6 months ago.

Exclusion Criteria

I have brain metastases but no ongoing symptoms without steroids.

It has been over 4 weeks since my last surgery or 2 weeks since my last radiation treatment.

I have a known DPD deficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive 5-FU/Leucovorin (LV) alone, with oxaliplatin or irinotecan or both, with dose adjustments based on PK assay results

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil (5-FU)

Trial Overview The study is testing whether adjusting doses of the chemotherapy drug 5-fluorouracil (5-FU) based on blood concentration levels can improve outcomes in metastatic colon cancer treatment. Other chemo regimens like FOLFIRI, Modified FOLFOX6, and mFOLFOXIRI are also being tested biweekly.

How Is the Trial Designed?

Group I: Chemotherapy with 5-FU/Leucovorin (LV) alone, with oxaliplatin or irinotecan or both Experimental Treatment 4 Interventions

Plasma specimens will be collected for the measurement of plasma 5-FU level from patients receiving 5-FU/LV alone, with oxaliplatin (mFOLFOX6) or irinotecan (FOLFIRI), or both (mFOLFOXIRI) chemotherapy. 5-FU doses will be modified based on the assay results.

Who Is Running the Clinical Trial?

Inova Health Care Services

Lead Sponsor

Trials

80

Recruited

22,700+

Published Research Related to This Trial

In a study of 1033 colorectal cancer patients treated with 5-fluorouracil (5FU) based adjuvant therapy, certain adverse events like neutropenia, nausea/vomiting, and mucositis were linked to better disease-free survival (DFS) and overall survival (OS).

Patients who experienced any grade of neutropenia had a 19% lower risk of disease progression, while those with nausea/vomiting had a 38% lower risk of death, suggesting that these adverse effects may serve as positive indicators of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of adverse events and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil and leucovorin: Is efficacy an impact of toxicity? Soveri, LM., Hermunen, K., de Gramont, A., et al.[2014]

The sensitivity to 5-fluorouracil (5-FU) in colorectal cancer patients varies significantly, with individual AUC(IR50) values ranging from less than 100 to over 1000 microg hr/ml, indicating that some patients may respond poorly to this treatment.

Achieving the individual AUC(IR50) is associated with significantly better relapse-free survival, suggesting that personalized chemotherapy duration based on 5-FU sensitivity could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study to predict optimal duration of chemotherapy with fluoropyrimidine by multi-point collagen gel droplet embedded drug sensitivity test. Tokunaga, Y., Sasaki, H., Ohnishi, T.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3259429/

Effectiveness of Adjuvant Chemotherapy with 5-FU ... In this study, the 5-year disease-free survival rate and the 5-year overall survival rate of patients with stage II colon cancer after adjuvant chemotherapy ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163725819301998

5-fluorouracil and other fluoropyrimidines in colorectal cancer 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for colorectal cancer (CRC) in the palliative and adjuvant settings.

3. nature.com nature.com/articles/s41467-020-19173-2

5-FU promotes stemness of colorectal cancer via p53 ... Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients.

4. asco.org asco.org/abstracts-presentations/ABSTRACT291535

Impact of empirically eliminating 5-fluorouracil (5-FU) ... This study aimed to assess the impact of empirically eliminating the 5-FU bolus and LV from first line treatment with mFOLFOX6 in mCRC.

5. ar.iiarjournals.org ar.iiarjournals.org/content/33/3/1053

Comparative Effectiveness of 5-Fluorouracil with and ... Our findings suggested no survival benefit with the addition of oxaliplatin to 5-FU modalities in treating CRC in practice.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11734475/

Cardiovascular safety of 5-fluorouracil and capecitabine in ... This study aimed to evaluate cardiovascular outcome among colorectal carcinoma patients treated with fluoropyrimidines.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804914009125

Association of adverse events and survival in colorectal ... With 5FU based adjuvant therapy overall survival benefit of 7–15% was achieved in stage III patients translating into 22–34% decrease in relative risk of death ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07042685

Study Details | NCT07042685 | Trial of 5-Fluorouracil (5FU) ... This is a phase II trial investigating the efficacy and safety of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib for patients with locally ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa032709

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant ... In previous trials, the addition of oxaliplatin to fluorouracil and leucovorin doubled the response rate and prolonged progression-free survival among patients ...