Clinical Trials /

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

NCT04361708

Description:

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).

Related Conditions:
  • Adenocarcinoma of Unknown Primary
  • Adenocarcinoma of the Gastroesophageal Junction
  • Ampulla of Vater Adenocarcinoma
  • Cholangiocarcinoma
  • Esophageal Adenocarcinoma
  • Gallbladder Adenocarcinoma
  • Gastric Adenocarcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety of Combining Irinotecan Chemotherapy With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IRB19-1292
  • NCT ID: NCT04361708

Conditions

  • Pancreatic Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma
  • Adenocarcinoma

Interventions

DrugSynonymsArms
OxaliplatinHigh Risk UGT1A1 genotype
DocetaxelHigh Risk UGT1A1 genotype
LeucovorinHigh Risk UGT1A1 genotype
IrinotecanHigh Risk UGT1A1 genotype
5-FluorouracilHigh Risk UGT1A1 genotype

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
High Risk UGT1A1 genotypeExperimental
  • Oxaliplatin
  • Docetaxel
  • Leucovorin
  • Irinotecan
  • 5-Fluorouracil
Intermediate Risk UGT1A1 genotypeExperimental
  • Oxaliplatin
  • Docetaxel
  • Leucovorin
  • Irinotecan
  • 5-Fluorouracil
Low Risk UGT1A1 genotypeExperimental
  • Oxaliplatin
  • Docetaxel
  • Leucovorin
  • Irinotecan
  • 5-Fluorouracil

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum dose tolerated
Time Frame:1 month
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Cumulative dose of each chemotherapy drug
Time Frame:4 months
Safety Issue:
Description:To determine the cumulative dose of each chemotherapy drug (irinotecan, 5-FU, oxaliplatin, docetaxel) administered in each genotype group over a period of 4 months (8 doses).
Measure:Total duration of therapy
Time Frame:18 months
Safety Issue:
Description:To determine the total duration of therapy, which would be administered perioperatively in future studies for the curative-intent setting.
Measure:Overall Response Rate
Time Frame:5 years
Safety Issue:
Description:To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.
Measure:Progression free survival rate
Time Frame:5 years
Safety Issue:
Description:To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.
Measure:Overall survival rate
Time Frame:5 years
Safety Issue:
Description:To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

Last Updated

April 23, 2020