Chemotherapy Combination for Cancer

(I-FLOAT Trial)

Overseen By Daniel Catenacci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must be taking: Pancreatic enzymes

Disqualifiers: Prior radiation, Inflammatory bowel, Neuropathy, others

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

Compensation: Varies

Number of Visits: 8

Duration: 4 months

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of chemotherapy drugs, including 5-Fluorouracil (5-FU), Docetaxel, Irinotecan, Leucovorin, and Oxaliplatin, to determine their safety when used together for treating certain advanced or metastatic cancers, such as pancreatic or gastroesophageal cancer. Researchers aim to discover if this drug combination can treat these cancers more effectively. Individuals with upper gastrointestinal cancers who maintain good organ function and have not undergone radiation or chemotherapy for metastatic disease may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial suggests that patients taking certain medications that interact with irinotecan should try to switch to other drugs if possible. It doesn't specify a complete stop of all current medications, but you should discuss your specific medications with the trial team.

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

Research shows that the combination of chemotherapy drugs in this trial has varying safety levels.

5-Fluorouracil (5-FU) is generally safe and does not increase the risk of major heart problems in patients with colorectal cancer, though it can cause early side effects that might affect survival rates.

Docetaxel is usually well-tolerated, with no major safety concerns for patients with early breast cancer.

Irinotecan can have significant side effects, with serious issues occurring in about 38% of patients and nearly 30% requiring hospitalization.

Leucovorin is often used with 5-FU to help reduce harmful side effects from other drugs.

Oxaliplatin can cause severe diarrhea, fatigue, and nerve damage, but it is considered safe when used with other 5-FU-based treatments.

This trial is in its early stages, so the safety of the drug combination is still under evaluation. However, each drug is approved for use in other cancer treatments, indicating that their individual safety is already established. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this chemotherapy combination for cancer because it specifically tailors treatment based on UGT1A1 genotype risk levels. Unlike standard chemotherapy regimens, which typically don't account for genetic variations, this approach personalizes treatment to potentially improve effectiveness and reduce side effects. By combining 5-Fluorouracil, Docetaxel, Irinotecan, Leucovorin, and Oxaliplatin, this regimen targets cancer cells more aggressively while allowing for adjustments based on genetic predisposition to drug metabolism. This innovative approach could lead to more precise and effective cancer treatments, marking a significant step forward in personalized medicine.

What evidence suggests that this trial's chemotherapy combination could be effective for cancer?

In this trial, participants will receive different treatments based on their UGT1A1 genotype risk level. Previous studies have shown that combining 5-Fluorouracil (5-FU) with other drugs can improve outcomes for certain cancers. Docetaxel, one of the drugs in this trial, has shown a high success rate, with many patients experiencing tumor reduction. Irinotecan has extended survival in some cancer patients, especially when combined with other treatments. Leucovorin enhances the effectiveness of 5-FU, increasing its potency against cancer cells. Additionally, oxaliplatin, when used in combination therapies, has improved survival rates in patients with colorectal cancer. Together, these drugs form a powerful mix that might offer a promising treatment option for cancer patients in this trial. ^{1 3 6 7 8}

Who Is on the Research Team?

Daniel Catenacci, MD

Principal Investigator

University of Chicago Medicine

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced gastrointestinal cancers who have a life expectancy over 3 months, good organ function, and no severe neuropathy or uncontrolled bleeding. They must not be pregnant or breastfeeding, haven't had major surgery recently, and can't have had prior chemotherapy for metastatic disease.

Inclusion Criteria

My blood counts and liver/kidney functions are within the required ranges.

Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential

I am willing to change my current medications to avoid interactions with irinotecan.

Exclusion Criteria

I have had radiation therapy for cancer before.

I have not had major surgery in the last 4 weeks.

I have experienced mild to severe diarrhea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the gFOLFOXIRITAX regimen, including irinotecan, 5-FU, leucovorin, oxaliplatin, and docetaxel, with genotype-guided dosing of irinotecan

4 months

8 doses administered

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Docetaxel
• Irinotecan
• Leucovorin
• Oxaliplatin

Trial Overview The I-FLOAT study tests the safety of combining multiple chemotherapies: Irinotecan with 5-Fluorouracil (5-FU), Leucovorin (a vitamin to enhance 5-FU's effect), Oxaliplatin, and Docetaxel in patients with specific types of gastrointestinal cancers.

How Is the Trial Designed?

Group I: Low Risk UGT1A1 genotype Experimental Treatment 5 Interventions

Group II: Intermediate Risk UGT1A1 genotype Experimental Treatment 5 Interventions

Group III: High Risk UGT1A1 genotype Experimental Treatment 5 Interventions

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

Approved in European Union as 5-FU for:

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

Approved in United States as 5-FU for:

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

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

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

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study of 50 patients with nonmetastatic colorectal cancer, adverse reactions were more frequent with the XELOX regimen (capecitabine combined with oxaliplatin), particularly neurotoxicity, thrombocytopenia, and neutropenia, compared to capecitabine monotherapy.

The type of capecitabine formulation (innovative vs. generic) did not significantly affect the safety profile; instead, the chemotherapy scheme used was the main factor influencing the occurrence of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Sánchez-Gundín, J., Torres-Suárez, AI., Fernández-Carballido, AM., et al.[2020]

Chemotherapy agents like fluorouracil and oxaliplatin can cause significant side effects in colorectal cancer treatment, but strategies like therapeutic drug monitoring and chronomodulation have shown promise in reducing these adverse effects in clinical trials.

Supportive measures, including specific medications and schedule adjustments, are essential for managing side effects such as myelosuppression and nausea, emphasizing the need for individualized patient care and teamwork among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer. Jansman, FG., Sleijfer, DT., de Graaf, JC., et al.[2018]

In a review of 61 patients with pancreatic adenocarcinoma treated with FOLFIRINOX, the regimen demonstrated clinical effectiveness with a median overall survival of 13.5 months, despite significant adverse events and dose modifications in over half of the treatment cycles.

The most common severe side effect was neutropenia, affecting 19.7% of patients, but there were no therapy-related deaths, indicating that while FOLFIRINOX can cause serious side effects, it remains a viable treatment option for both metastatic and locally advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. Peddi, PF., Lubner, S., McWilliams, R., et al.[2022]

Oxaliplatin, a new platinum analog, shows high effectiveness in treating metastatic colorectal cancer, particularly when used in combination with 5-FU and leucovorin, which has led to its approval in Europe for first- and second-line treatments.

This ongoing compassionate-use study aims to provide oxaliplatin to patients in the United States who have no adequate second- or third-line therapy options available, highlighting the urgent need for safety data and FDA approval for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin with 5-FU or as a single agent in advanced/metastatic colorectal cancer. Mitchell, EP.[2018]

Oxaliplatin, when used in combination with 5FU and leucovorin, shows significantly higher response rates in previously untreated patients, achieving objective response rates between 51% and 66% and improving overall survival to 16-19 months.

The combination therapy not only enhances efficacy but may also reduce dose-limiting toxicities, such as sensory neurotoxicity, and has enabled some patients with initially unresectable metastases to undergo complete surgical removal of metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxaliplatin in combination with 5-fluoro-uracil and folinic acid as treatment of metastatic colorectal cancer]. André, T., Louvet, C., Maindrault-Goebel, F., et al.[2018]

Capecitabine, an oral fluoropyrimidine, has been shown to achieve superior response rates and equivalent overall survival compared to traditional intravenous 5-FU plus leucovorin in metastatic colorectal cancer, making it a preferred treatment option.

Recent trials, including the Xeloda Adjuvant Chemotherapy Trial (X-ACT), confirm that capecitabine is at least as effective and safer than IV 5-FU/LV for adjuvant treatment in patients with resected stage III colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine: bridging the Atlantic divide in colon cancer treatment. Van Cutsem, E., Verslype, C., Tejpar, S.[2018]

5-Fluorouracil (5-FU) is the primary treatment for colorectal cancer, and its effectiveness can be enhanced by combining it with agents like leucovorin, which has shown improved response rates and potential survival benefits compared to 5-FU alone.

Recent trials indicate that infusional regimens of 5-FU are the least toxic and may be more effective, leading to better quality of life for patients, with future research focusing on optimizing these delivery methods for maximum benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomodulation of Fluorouracil in colorectal cancer. Ardalan, B., Luis, R., Jaime, M., et al.[2019]

A 42-year-old woman with metastatic breast cancer experienced allergic reactions to capecitabine, leading to its discontinuation, but she tolerated fluorouracil without any adverse effects during treatment.

Fluorouracil can be safely used in patients with mild allergic reactions to capecitabine, as demonstrated by this case where the patient had no complications after switching treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorouracil for allergic reactions to capecitabine. Liu, CY.[2017]

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]

A sequential combination therapy using docetaxel, followed by flavopiridol, and then 5-fluorouracil (5-FU) showed maximum cytotoxicity against HCT116 colon cancer cells, significantly inhibiting tumor growth and promoting apoptosis.

In xenograft models, this treatment schedule not only delayed tumor growth but also improved survival rates, emphasizing the importance of administration timing in enhancing the efficacy of these chemotherapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts with docetaxel, flavopiridol, and 5-fluorouracil. Guo, J., Zhou, AW., Fu, YC., et al.[2018]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

A phase II study involving 43 patients with advanced gastrointestinal tumors showed that capecitabine combined with either irinotecan or oxaliplatin is effective in treating colorectal and other GI cancers, demonstrating significant clinical activity as both first-line and salvage therapy.

The combination therapies exhibited an excellent safety profile, with manageable grade 3/4 toxicities primarily limited to diarrhea, and no severe myelosuppression observed, indicating that these regimens are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine/irinotecan and capecitabine/oxaliplatin in advanced gastrointestinal cancers. Jordan, K., Kellner, O., Kegel, T., et al.[2019]

Infusional 5-fluorouracil combined with leucovorin shows a higher response rate and better toxicity profile compared to the standard bolus regimen, although it does not improve median survival rates in metastatic colorectal cancer.

Ongoing studies are exploring new drug combinations with 5-fluorouracil, such as oxaliplatin and CPT-11, which may offer improved efficacy over the current standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in fluoropyrimidine therapy for gastrointestinal cancer. Van Cutsem, E., Peeters, M.[2019]

In a study using the KPL-4 human breast cancer model, combining docetaxel with oral fluoropyrimidines (5'-dFUrd or tegafur) significantly enhanced tumor growth inhibition and reduced serum IL-6 levels compared to either treatment alone.

The combination treatment also decreased the expression of thymidine phosphorylase in tumors, suggesting that docetaxel may enhance the effectiveness of fluoropyrimidines while also potentially alleviating cancer-related cachexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts. Yamamoto, S., Kurebayashi, J., Kurosumi, M., et al.[2019]

Citations

1. 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.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0753332221000706

5-Fluorouracil (5-FU) resistance and the new strategy to ... It is reported that the response rate of 5-FU based first-line chemotherapy in advanced CRC cases is still only 10–15 %. But when 5-FU is combined with other ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8013832/

5‐Fluorouracil efficacy requires anti‐tumor immunity triggered ... Upon 5‐FU treatment, tumor burden was reduced significantly in both STING+/+ and STING−/− hosts, with the reduction modestly less prominent in ...

4. news.mit.edu news.mit.edu/2024/cancer-biologists-discover-new-mechanism-old-drug-1007

Cancer biologists discover a new mechanism for an old drug Instead, combining 5-FU with drugs that affect RNA synthesis could make it more effective in patients with GI cancers, the researchers say. “Our ...

5. nature.com nature.com/articles/s41598-025-86523-9

Exploring the efficacy of fluorouracil and platinum based ... The median OS was 8.2 months (95% CI, 2.5–13.9), and the estimated OS rates were 66.7% (95% CI, 51.5–78.1%) at 6 months and 46.8% (95% CI, 32.1– ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK549808/

Fluorouracil - StatPearls - NCBI Bookshelf The overall response rate of advanced colorectal cancer to fluorouracil monotherapy is only 10% to 15% and 40% to 50% when combined with other chemotherapeutic ...

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. 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 ...