mFOLFIRINOX for Stomach Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Chicago

Must not be taking: CYP3A4 substrates

Disqualifiers: Previous malignancy, Inflammatory bowel disease, Diarrhea, Neuropathy, 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: 3

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies genetic analysis-guided irontecan hydrochloride dosing of modified fluorouracil, irinotecan hydrochloride, leucovorin calcium, oxaliplatin (mFOLFIRINOX) in treating patients with gastroesophageal or stomach cancer that has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin calcium may also help fluorouracil work better. Genetic analysis may help doctors determine what dose of irinotecan hydrochloride patients can tolerate.

Will I have to stop taking my current medications?

The trial suggests that if you are taking medications that affect a specific liver enzyme (CYP3A4), you should try to switch to other drugs to avoid interactions with the trial medication. It doesn't specify a need to stop other medications, but it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug mFOLFIRINOX for stomach cancer?

Research shows that a similar drug combination, mFOLFIRI, which includes some of the same components as mFOLFIRINOX, has been effective as a second-line treatment for advanced gastric (stomach) cancer, especially after other treatments have failed. ^{1 2 3 4 5}

Is mFOLFIRINOX safe for humans?

The mFOLFIRINOX treatment, which includes 5-fluorouracil, irinotecan, and oxaliplatin, has been used in advanced pancreatic cancer and is known to have some side effects, but it is generally considered safe for fit patients. It has been evaluated for safety in other cancers, like gastric and colorectal cancer, showing it can be tolerated with careful monitoring. ^{1 2 4 6 7}

What makes the mFOLFIRINOX drug unique for stomach cancer?

The mFOLFIRINOX drug is unique for stomach cancer because it combines four different chemotherapy agents (fluorouracil, leucovorin, irinotecan, and oxaliplatin) that work together to target cancer cells more effectively. This combination is adapted from its use as a first-line treatment in advanced pancreatic cancer, offering a novel approach for stomach cancer where standard treatments may not be well-established. ^{1 2 3 8 9}

Research Team

Daniel Catenacci, MD

Principal Investigator

University of Chicago Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced gastroesophageal or stomach cancer without distant spread. They must be fit for surgery, have certain blood counts and organ functions within set limits, not be pregnant, agree to use birth control, and can't have other cancers or serious illnesses that could interfere with the study.

Inclusion Criteria

My cancer is a type of stomach or esophagus cancer confirmed by tissue analysis.

I am a candidate for surgery aimed at curing my condition.

Specific blood count requirements (ANC, Hemoglobin, Platelets)

Exclusion Criteria

I have moderate to severe nerve damage.

Pregnancy or breastfeeding

Serious underlying medical or psychiatric illnesses

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Therapy

Patients receive oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil intravenously. Courses repeat every 2 weeks for 4 courses.

8 weeks

Surgery

Patients undergo conventional surgery.

Post-operative Therapy

Beginning 5-10 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil intravenously. Courses repeat every 2 weeks for 4 more courses.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Fluorouracil
• Irinotecan Hydrochloride
• Leucovorin Calcium
• Oxaliplatin

Trial Overview The trial tests a personalized dose of Irinotecan in the mFOLFIRINOX regimen (a combination of chemotherapy drugs) based on genetic analysis. The goal is to see if tailoring the dose improves tolerance and effectiveness against locally advanced gastroesophageal or stomach cancer.

Participant Groups

Group I: Treatment (mFOLFIRINOX, surgery) Experimental Treatment 5 Interventions

PREOPERATIVE THERAPY: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV over 46 hours continuously on day 1. Courses repeat every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo conventional surgery. POST-OPERATIVE THERAPY: Beginning 5-10 weeks after surgery, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV over 46 hours continuously on day 1. Courses repeat every 2 weeks for 4 more courses in the absence of disease progression or unacceptable toxicity.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) regimen showed a response rate of 29.7% and a clinical benefit rate of 57.2% in 91 patients with advanced gastric cancer, indicating its efficacy as a second-line treatment.

Despite its effectiveness, the mFOLFIRI regimen was associated with significant adverse events, including neutropenia in 18.7% of patients, highlighting the need for careful monitoring and potential dose modifications during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. Ramaswamy, A., Ostwal, V., Gupta, K., et al.[2022]

In a study of 32 patients with advanced gastric cancer, modified FOLFIRI chemotherapy was found to be tolerable, with a disease control rate of 43.8%, but it showed a low response rate with only 9.4% achieving partial response.

The median overall survival after starting FOLFIRI was 5.84 months, indicating that while the treatment is manageable, its effectiveness as a second-line option after FOLFOX is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer. Jeon, EK., Hong, SH., Kim, TH., et al.[2021]

In a study of 59 patients with advanced gastric cancer, both irinotecan (CPT-11) monotherapy and the combination of CPT-11 with 5-fluorouracil (mFOLFIRI) showed similar efficacy, with objective response rates of 17.2% and 20.0%, respectively, indicating that neither treatment was significantly better than the other.

The addition of 5-FU and leucovorin to CPT-11 did not lead to improved progression-free survival or overall survival compared to CPT-11 alone, suggesting that the combination therapy may not provide additional benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of biweekly irinotecan monotherapy or a combination of irinotecan plus 5-fluorouracil/leucovorin (mFOLFIRI) in patients with metastatic gastric adenocarcinoma refractory to or progressive after first-line chemotherapy. Sym, SJ., Hong, J., Park, J., et al.[2022]

The FOLFIRI chemotherapy regimen demonstrated modest antitumor activity in advanced gastric cancer, with an overall response rate of 9.6% and a median overall survival of 5.6 months among 158 patients treated after failing other therapies.

The treatment was associated with significant myelosuppression (36.7% of patients experiencing grade 3/4 toxicity), but factors such as good performance status, fewer metastatic sites, and longer intervals between treatments were identified as predictors of better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival. Kang, EJ., Im, SA., Oh, DY., et al.[2022]

The modified FOLFIRI regimen, which combines low doses of leucovorin and 5-fluorouracil with irinotecan, showed an overall response rate of 38.6% in 44 patients with advanced gastric cancer, indicating its efficacy as a first-line treatment.

The treatment was found to be safe, with manageable toxicities; major side effects included grade 1 to 2 anemia and neutropenia, but there were no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of irinotecan with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as first line therapy for patients with recurrent or metastatic gastric cancer. Kim, BG., Oh, SY., Kwon, HC., et al.[2018]

The combination of FOLFIRI and aflibercept was found to be active and tolerable in treating metastatic colorectal cancer (mCRC), with an objective response rate of 46.6% among 73 patients, indicating potential effectiveness in this patient population.

Despite its activity, the regimen did not surpass historical benchmarks for efficacy in chemotherapy-naive patients, with a 12-month progression-free survival rate of only 21.9% and a median overall survival of 20.9 months, suggesting that while it may help some patients, it may not be a significant improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. Pentheroudakis, G., Kotoula, V., Koliou, GA., et al.[2019]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

In a study involving 105 patients with metastatic colorectal cancer, arfolitixorin was found to be well-tolerated and showed potential to enhance the efficacy of 5-fluorouracil (5-FU), with 15.8% of patients achieving a partial response after 8 weeks of treatment.

Arfolitixorin, an immediately active form of folate, may improve treatment outcomes, especially in patients with low folate pathway gene expression, and can be easily integrated into existing chemotherapy regimens with minimal adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer. Carlsson, G., Koumarianou, A., Guren, TK., et al.[2022]

In a study of 198 patients with advanced pancreatic cancer, the SOXIRI chemotherapy regimen showed similar overall survival (12.1 months) and progression-free survival (6.5 months) compared to the standard mFOLFIRINOX regimen (11.2 months and 6.8 months, respectively), indicating comparable efficacy.

While both regimens had similar safety profiles, SOXIRI was associated with a higher incidence of anemia (41.4% vs. 24%), suggesting that while effective, it may have specific side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. Li, X., Huang, J., Wang, F., et al.[2023]

References

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

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

A randomized phase II study of biweekly irinotecan monotherapy or a combination of irinotecan plus 5-fluorouracil/leucovorin (mFOLFIRI) in patients with metastatic gastric adenocarcinoma refractory to or progressive after first-line chemotherapy. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival. [2022]

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

A phase II study of irinotecan with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as first line therapy for patients with recurrent or metastatic gastric cancer. [2018]

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

AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. [2023]