Oxaliplatin + Fluorouracil for Colorectal Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arjun Mittra

Must not be taking: Investigational drugs

Disqualifiers: BRAF mutation, Appendiceal tumors, others

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

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the safest way to use two drugs, oxaliplatin and fluorouracil, to treat colorectal cancer that has spread to the abdomen. Both drugs attack cancer cells, but this trial tests their effectiveness when delivered directly into the abdomen. The goal is to determine if this method can safely target cancer in that specific area. Suitable candidates for this trial have colorectal cancer that has spread to the peritoneal cavity (the area around the abdominal organs) and have not undergone certain types of prior surgeries for their cancer.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on anticoagulation or antiplatelet agents, you may need to hold them for surgical procedures, as decided by your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found that administering oxaliplatin directly into the peritoneal cavity (the space in the abdomen between the muscles and organs) at a dose of 92 mg/m² was safe. Researchers treated 251 patients and observed that only 7.7% experienced serious side effects. Research has shown that fluorouracil is generally well-tolerated and does not increase the risk of major heart problems in patients with colorectal cancer. Both oxaliplatin and fluorouracil have FDA approval for treating colorectal cancer in other forms, supporting their safety. However, this trial is testing a new method of administering these drugs, so their safety is still being closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment using oxaliplatin and fluorouracil for colorectal cancer because it introduces a new delivery method: intraperitoneal (IP) infusion. Unlike traditional intravenous methods, IP infusion delivers chemotherapy directly to the abdominal cavity, targeting cancer cells more effectively and potentially reducing systemic side effects. This approach could enhance drug concentration at the tumor site, offering a promising alternative to existing treatments like intravenous chemotherapy, which includes drugs like FOLFOX and FOLFIRI. By concentrating the treatment where it’s needed most, this method may improve outcomes for patients with colorectal cancer.

What evidence suggests that this treatment might be an effective treatment for colorectal cancer with peritoneal metastasis?

Research has shown that oxaliplatin and fluorouracil work well together to treat colorectal cancer. In this trial, participants will receive these drugs directly into the belly (intraperitoneal) to better target cancer that has spread there. Studies suggest this method could be safe and effective. Oxaliplatin damages the DNA of cancer cells, while fluorouracil prevents them from making DNA. Together, these drugs have shown promise in managing cancer that has spread to the belly area. ^{6 7 8 9 10}

Who Is on the Research Team?

Arjun Mittra

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with colorectal cancer that has spread to the lining of the abdomen (peritoneal metastasis). They should not have had certain previous treatments, must be expected to live at least 6 months, and have good organ function. Women who can bear children need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Anticipated life expectancy of ≥ 6 months

I am willing to use birth control during and for 9 months after the study.

I haven't had systemic therapy for metastatic colorectal cancer but may have had adjuvant chemotherapy over 6 months ago.

Exclusion Criteria

I do not have any severe illnesses that could interfere with the study.

I have severe liver disease with complications like confusion or fluid in the abdomen.

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intraperitoneal oxaliplatin and fluorouracil over 1-2 hours on days 1 and 15 of each cycle. Cycles repeat every 4 weeks for up to 16 weeks.

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes monitoring for adverse events and disease progression.

30 days

1 visit (in-person)

Long-term Follow-up

Participants with confirmed disease progression or who start a new anti-cancer therapy are followed up every 12 weeks until death, withdrawal of consent, or end of study.

Every 12 weeks until end of study

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Intraperitoneal Oxaliplatin

Trial Overview The trial tests intraperitoneal oxaliplatin and fluorouracil's safety, side effects, and best dose. These drugs are given directly into the abdominal space in patients with peritoneal metastases from colorectal cancer. This method is experimental despite both drugs being FDA-approved for colorectal cancer treatment.

How Is the Trial Designed?

Group I: Treatment (oxaliplatin, 5FU) Experimental Treatment 8 Interventions

Patients undergo placement of indwelling IP port for chemotherapy infusion. Patients receive oxaliplatin and 5FU over 1-2 hours via IP infusion on days 1 and 15 of each cycle. Cycles repeat every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy, biopsy, CT/MRI, and collection of blood samples at screening and on study and undergo collection of IP fluid samples on study.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Arjun Mittra

Lead Sponsor

Trials

1

Recruited

20+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 206 patients with advanced colorectal carcinoma who had previously failed 5-FU-based therapy, the addition of oxaliplatin to 5-FU +/- folinic acid resulted in a 25.5% objective response rate, demonstrating its efficacy as a salvage therapy.

The median overall survival for patients receiving oxaliplatin combined with 5-FU +/- FA was 9.6 months, indicating that this treatment can provide significant benefits for patients resistant to prior fluoropyrimidine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program. Brienza, S., Bensmaïne, MA., Soulié, P., et al.[2020]

Adjuvant therapy using 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine has significantly improved 3-year disease-free survival rates in stage III colorectal cancer patients, indicating its efficacy in early disease stages.

The addition of oxaliplatin to 5-FU-based regimens has been confirmed to enhance disease-free survival, establishing it as a standard treatment alongside other chemotherapy options for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid evolution in colorectal cancer: therapy now and over the next five years. de Gramont, A.[2007]

The combination of oxaliplatin (OXA) with 5-fluorouracil (5-FU) and leucovorin (LV) alongside concurrent radiotherapy was found to be feasible and effective in treating 22 patients with unresectable rectal cancer, leading to a median overall survival of 19.5 months.

Despite some reported toxicities, including diarrhea and neutropenia, the treatment was manageable, with 12 out of 16 patients undergoing successful surgeries, indicating a promising approach for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study. Carraro, S., Roca, EL., Cartelli, C., et al.[2019]

In a study of 9 Korean patients with advanced colorectal cancer, the pharmacokinetics of oxaliplatin showed higher maximum concentration ratios in total plasma compared to other ethnic groups, indicating potential differences in drug metabolism.

The plasma concentrations of 5-fluorouracil (5-FU) varied significantly among patients, suggesting that individual responses to treatment may differ widely, which could impact overall antitumor efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer. Cho, HK., Lee, ES., Lee, JW., et al.[2018]

The combination of traditional chemotherapy agents like fluorouracil (5FU) with newer drugs such as irinotecan and oxaliplatin has significantly improved treatment effectiveness for colorectal cancer, leading to better patient outcomes.

Emerging targeted therapies are showing promise in reducing toxicity compared to traditional chemotherapy, and their integration into treatment protocols may extend survival rates for metastatic colorectal cancer patients from 2 to potentially 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The modern treatment of colorectal cancer. Present and future]. András, C., Farczádi, E., Szántó, J.[2018]

Fluorouracil has been effectively used for over 20 years to alleviate symptoms in patients with metastatic colorectal carcinoma, but researchers are exploring ways to enhance its effectiveness.

Prolonged infusion of fluorouracil, combined with leucovorin, improves its ability to inhibit cancer cell replication, potentially leading to better response and survival rates in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of metastatic colorectal carcinoma. Recent advances in use of fluorouracil. Treat, J., Joseph, RR.[2019]

Oxaliplatin is a promising treatment for colorectal cancer (CRC) that works well in combination with 5-fluorouracil (5-FU), even in cases where tumors are resistant to 5-FU, as shown in controlled phase III trials.

With its excellent safety profile and unique mechanism of action, oxaliplatin can be effectively combined with other chemotherapy agents, and ongoing studies aim to optimize its use in CRC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a new therapeutic option in colorectal cancer. Cvitkovic, E., Bekradda, M.[2022]

Oxaliplatin shows effectiveness as a standalone treatment for colorectal cancer, both in patients who have not received chemotherapy and those who have progressed after 5-fluorouracil (5-FU) treatment.

The combination of oxaliplatin with UFT (uracil plus tegafur) and oral calcium folinate has the potential to enhance treatment outcomes for advanced colorectal cancer, leveraging the known synergy between oxaliplatin and 5-FU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin and UFT/oral calcium folinate for advanced colorectal carcinoma. Hoff, PM., Pazdur, R.[2018]

5-fluorouracil (5-FU) is a commonly used anticancer drug for colorectal cancer, but it can rarely cause neurotoxic side effects, including encephalopathy, seizures, and delirium.

In cases of 5-FU-induced neuropsychiatric complications, especially if ammonia levels are high, lactulose may be an effective initial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The confused cancer patient: a case of 5-fluorouracil-induced encephalopathy. Cheung, WY., Fralick, RA., Cheng, S.[2021]

The combination of oxaliplatin with 5-fluorouracil and folinic acid (known as FOLFOX) is more effective than the alternative treatment (IFL) for first-line therapy in advanced colorectal cancer, showing superior median survival rates and tumor response, while also having fewer severe side effects except for increased peripheral neuropathy.

For second-line treatment, FOLFOX is a reasonable option for patients who cannot use irinotecan, and adding bevacizumab to the FOLFOX regimen may provide additional survival benefits after progression on initial therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oxaliplatin combined with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer. Jonker, D., Rumble, RB., Maroun, J.[2021]

In a study of 267 patients with stage III colorectal cancer treated with the mFLOX regimen, the 2-year disease-free survival rate was 74.9%, indicating that the combination of oxaliplatin and bolus 5-FU is effective in a community setting, similar to clinical trial results.

However, the study found a higher risk of death in patients over 70 years old, suggesting that adjuvant oxaliplatin should be used cautiously, particularly in older patients, due to a significant incidence of Grade ≥3 toxicities, including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of a Modified FLOX Adjuvant Regimen for Patients With Stage III Colorectal Cancer Treated in the Community. Protásio, BM., Matutino, A., Lage, LV., et al.[2018]

Oxaliplatin is an effective treatment for advanced colorectal cancer, showing activity as both a first- and second-line therapy, and is well tolerated when combined with fluorouracil/leucovorin.

Unlike other platinum-based drugs, oxaliplatin has a lower risk of kidney and ear damage, but it can cause acute and chronic neurosensory symptoms, which are manageable and reversible upon stopping the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oxaliplatin in the treatment of colorectal cancer. Haller, DG.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06269978

Study Details | NCT06269978 | Intraperitoneal Oxaliplatin ... This phase I trial tests the safety, side effects, and best dose of intraperitoneal oxaliplatin and fluorouracil in treating patients with colorectal cancer ...

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

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant ... Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2741642/

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin ... The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224007042

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5- ... Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A ...

5. trialx.com trialx.com/clinical-trials/listings/309476/intraperitoneal-oxaliplatin-and-fluorouracil-for-the-treatment-of-patients-with-peritoneal-metastases-from-colorectal-cancer/

Intraperitoneal Oxaliplatin and Fluorouracil for the ... Giving oxaliplatin and fluorouracil directly into the peritoneal space may be a safe and effective way of treating patients with peritoneal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11639909/

Long-Term Outcomes of 5-Fluorouracil-Related Early-Onset ... The median overall survival was 2.5 years in those who experienced early-onset toxicity from 5-FU during their first FOLFOX/FOLFIRINOX cycle.

7. cardiooncologyjournal.biomedcentral.com cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-024-00294-2

Cardiovascular safety of 5-fluorouracil and capecitabine in ... Fluoropyrimidine use in patients with colorectal carcinoma did not increase the risk of MACE, cardiovascular death, or other specific cardiovascular conditions.

8. 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 ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39010662/

Adverse drug events associated with fluorouracil use in ... Our study provides a comprehensive analysis of 5-FU's safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

10. 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 ...