Safety of Combining Irinotecan With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies

NCT04361708 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB19-1292
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the proposed study is to establish the safety of combining irinotecan chemotherapy with 5-FU, leucovorin/folinic acid, oxaliplatin, and docetaxel (abbreviated as the I-FLOAT study of gFOLFOXIRITAX) chemotherapies (leucovorin/folinic acid is a vitamin to make 5-FU work well).

Conditions

Pancreatic Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• The maximum dose tolerated

  To determine the maximum tolerated dose in the first month of therapy in each of the three main genotype groups (low, intermediate, and high risk) using genotype-guided dosing of irinotecan as part of the I-FLOAT regimen

  1 month

Secondary Outcomes (5)

• Cumulative dose of each chemotherapy drug

  4 months

• Total duration of therapy

  18 months

• Overall Response Rate

  5 years

• Progression free survival rate

  5 years

• Overall survival rate

  5 years

Study Arms (3)

High Risk UGT1A1 genotype

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Docetaxel; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil

Intermediate Risk UGT1A1 genotype

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Docetaxel; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil

Low Risk UGT1A1 genotype

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Docetaxel; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil

Interventions

Oxaliplatin DRUG

Oxaliplatin will be administered on day 1 of each cycle at 85mg/kg. The drugs will be given through the patient's Mediport. It will be given once every 14 days (2 weeks), on days 1 and will be continued for 8 doses (4 months)

High Risk UGT1A1 genotype; Intermediate Risk UGT1A1 genotype; Low Risk UGT1A1 genotype

Docetaxel DRUG

Docetaxel will be administered on day 1 of each cycle at 25mg at dose level 1; 37.5 at dose level 2. The drugs will be given through the patient's Mediport.It will be given once every 14 days (2 weeks), on days 1 and will be continued for 8 doses (4 months)

High Risk UGT1A1 genotype; Intermediate Risk UGT1A1 genotype; Low Risk UGT1A1 genotype

Leucovorin DRUG

Leucovorin will be administered on day 1 of each cycle at 400mg/kg. The drugs will be given through the patient's Mediport. It will be given once every 14 days (2 weeks), on days 1 and will be continued for 8 doses (4 months)

High Risk UGT1A1 genotype; Intermediate Risk UGT1A1 genotype; Low Risk UGT1A1 genotype

Irinotecan DRUG

Irinotecan will be administered on day 1 of each cycle at 120mg/m2 for low risk group, 105mg/m2 for intermediate risk group, 45mg/m2 for high risk group . The drugs will be given through the patient's Mediport. It will be given once every 14 days (2 weeks), on days 1 and will be continued for 8 doses (4 months)

High Risk UGT1A1 genotype; Intermediate Risk UGT1A1 genotype; Low Risk UGT1A1 genotype

5-Fluorouracil DRUG

5-FU is given as a continuous intravenous infusion over 2 days. Patient can receive the 2-day infusion as an outpatient. On day 3 of each cycle, the patient will return to the infusion center to have the infusion hook-up disconnected.

High Risk UGT1A1 genotype; Intermediate Risk UGT1A1 genotype; Low Risk UGT1A1 genotype

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status =1
• Life expectancy \> 3 months
• 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
• Measurable or non-measurable disease will be allowed.
• Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
• Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential
• 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.

You may not qualify if:

• Prior radiation therapy for any cancer.
• Prior chemotherapy for metastatic disease Recurrence of disease within 6 months of perioperative chemotherapy are eligible if other eligibility criteria are met
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• 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.
• Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0.
• Documented brain metastases
• Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment.
• Active uncontrolled bleeding.
• Pregnancy or breastfeeding.
• Major surgery within 4 weeks.
• 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Oxaliplatin; Docetaxel; Leucovorin; Irinotecan; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Daniel Catenacci, MD

  University of Chicago Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Catenacci, MD

CONTACT

773-702-7596; dcatenacci@medicine.bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 24, 2020
• Study Start: May 8, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

US (1)