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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a chemotherapy drug combination called mFOLFIRINOX for individuals with stomach or gastroesophageal cancer that has spread locally. The treatment includes several drugs—Fluorouracil (5-FU), Irinotecan Hydrochloride, Leucovorin Calcium, and Oxaliplatin—to stop tumor growth, kill cancer cells, or prevent their spread. Genetic tests will guide doctors in selecting the appropriate dose for each participant. This trial may suit those diagnosed with locally advanced stomach cancer, who have had an endoscopic ultrasound showing specific tumor growth, and are eligible for surgery with curative intent. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

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 is the safety track record for these treatments?

Research has shown that the mFOLFIRINOX treatment for advanced cancer is generally well-tolerated. While patients may experience side effects, studies have found no unexpected harmful effects when used as a first treatment option.

In a study on the safety of similar treatments, one patient experienced severe tumor bleeding, and five patients had significant diarrhea. However, these side effects are uncommon.

Overall, mFOLFIRINOX is considered safe, especially since it is being tested in a Phase 4 trial. This phase typically indicates that the treatment has already been approved for some use and continues to be monitored for safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about mFOLFIRINOX for stomach cancer because it combines four powerful chemotherapy drugs: fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin. This combination treatment is unique as it is given both before and after surgery, aiming to shrink tumors more effectively and reduce the chance of cancer returning. Unlike standard treatments that typically focus on either pre-operative or post-operative chemotherapy, mFOLFIRINOX offers a comprehensive approach that could enhance survival rates and improve patient outcomes.

What is the effectiveness track record for mFOLFIRINOX in treating stomach cancer?

Research has shown that mFOLFIRINOX, a combination of four chemotherapy drugs, effectively treats advanced stomach cancer. In this trial, participants will receive mFOLFIRINOX both before and after surgery. Studies have found that this treatment can effectively stop tumors from growing. Specifically, FOLFIRINOX has successfully shrunk tumors in some patients. Most people tolerate the side effects, which are usually manageable. However, some studies suggest it might not significantly extend survival compared to other similar treatments for certain types of stomach cancer. Still, its ability to control the spread of cancer makes it a strong treatment option. ^{1 2 3 4 6}

Who Is on the Research Team?

Daniel Catenacci, MD

Principal Investigator

University of Chicago Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

My genetic test shows I have a UGT1A1 variant that is not *1 or *28.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2848749/

Outcomes of Modified FOLFOX-6 as First Line Treatment in ... The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02002195

Modified Folinic Acid-Fluorouracil-Oxaliplatin Regimen ... In gastric cancer patients, oxaliplatin has shown a more favorable toxicity profile than cisplatin . A combination chemotherapy of 5-FU with oxaliplatin, mainly ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7260693/

FOLFIRINOX for the Treatment of Advanced ... We conclude that the triple-drug FOLFIRINOX regimen is associated with an impressive ORR and no unexpected toxic effects in first-line treatment of advanced ...

4. onclive.com onclive.com/view/mfolfirinox-does-not-significantly-improve-survival-vs-mfolfox6-in-her2-metastatic-gastric-gej-adenocarcinoma

mFOLFIRINOX Does Not Significantly Improve Survival Vs ... IRIGA trial comparing mFOLFIRINOX vs mFOLFOX6 shows mixed results in HER2-negative metastatic gastric and GEJ adenocarcinoma.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37557-X/fulltext

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil ... Background: This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients.

6. sciencedirect.com sciencedirect.com/science/article/pii/S092375341937557X

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil ... One (2%) patient had severe tumor bleeding and five (10%) patients experienced grade 3 diarrhea. Conclusions: The modified FOLFOXIRI combination chemotherapy ...