Combining irinotecan with multiple chemotherapy agents for cancer treatment

A Phase 1 Dose Finding Study of the gFOLFOXIRITAX Regimen Using UGT1A1 Genotype-directed Irinotecan With Fluorouracil, Leucovorin, Oxaliplatin and Taxotere in Patients With Untreated Advanced Upper Gastrointestinal Adenocarcinomas: The I-FLOAT Study

This study is testing a new combination of chemotherapy drugs, including irinotecan, to see if it can safely help people with advanced gastrointestinal cancers like pancreatic and gastroesophageal junction adenocarcinoma who haven't had success with other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Chicago (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT04361708 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of a new chemotherapy regimen that combines irinotecan with 5-FU, leucovorin, oxaliplatin, and docetaxel for patients with advanced gastrointestinal cancers. The approach focuses on patients with pancreatic adenocarcinoma and gastroesophageal junction adenocarcinoma, among others. By assessing the safety profile of this combination, the study seeks to determine if it can be a viable treatment option for those who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed locally advanced or metastatic gastrointestinal adenocarcinomas.

Not a fit: Patients with severe organ dysfunction or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced gastrointestinal cancers.

How similar studies have performed: Other studies have shown promise in combining chemotherapy agents for similar conditions, but this specific combination is being evaluated for the first time.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, gastroesophageal adenocarcinoma, cholangiocarcinoma, gallbladder adenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with upper GI primary suspected), or other primary GI malignancy for which the treating physician feels that I-FLOAT is a reasonable therapeutic option.
2. Patients with a history of obstructive jaundice due to the primary tumor must have resolved to \<1.5 X upper limit of normal and a metal biliary stent in place
3. Age greater than or equal to 18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status =1
5. Life expectancy \> 3 months
6. Adequate organ function, as defined by each of the following:

   Absolute neutrophil count (ANC) = 1500/uL Hemoglobin \> 9g/dL (transfusion permitted with stability for \> 1 week) Platelets \> 100,000/uL Total bilirubin = 1.5 mg/dL AST and ALT = 2.5 X upper limit of normal; alkaline phosphatase = 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis.

   AST and ALT = 5 X upper limit of normal if hepatic metastases are present. Creatinine = 1.5 mg/dL
7. Measurable or non-measurable disease will be allowed.
8. Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
9. Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential
10. Patients taking substrates, inhibitors, or inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan.

Exclusion Criteria:

1. Prior radiation therapy for any cancer.
2. Prior chemotherapy for metastatic disease Recurrence of disease within 6 months of perioperative chemotherapy are eligible if other eligibility criteria are met
3. Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
4. Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v. 4.0\*). Pancreatic cancer patients with clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme replacement.
5. Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0.
6. Documented brain metastases
7. Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment.
8. Active uncontrolled bleeding.
9. Pregnancy or breastfeeding.
10. Major surgery within 4 weeks.
11. Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%, and meets all other eligibility criteria.

Where this trial is running

Chicago, Illinois

• The University of Chicago — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Daniel Catenacci, MD — University of Chicago Medicine
• Study coordinator: Daniel Catenacci, MD

Conditions Pancreatic Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Adenocarcinoma