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

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ClinicalTrials.gov Identifier: NCT04361708
Recruitment Status : Not yet recruiting
First Posted : April 24, 2020
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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).

Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Adenocarcinoma Drug: Oxaliplatin Drug: Docetaxel Drug: Leucovorin Drug: Irinotecan Drug: 5-Fluorouracil Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 15, 2020
Estimated Primary Completion Date : September 15, 2023
Estimated Study Completion Date : September 15, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High Risk UGT1A1 genotype Drug: Oxaliplatin
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)

Drug: Docetaxel
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)

Drug: Leucovorin
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)

Drug: Irinotecan
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)

Drug: 5-Fluorouracil
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.

Experimental: Intermediate Risk UGT1A1 genotype Drug: Oxaliplatin
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)

Drug: Docetaxel
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)

Drug: Leucovorin
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)

Drug: Irinotecan
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)

Drug: 5-Fluorouracil
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.

Experimental: Low Risk UGT1A1 genotype Drug: Oxaliplatin
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)

Drug: Docetaxel
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)

Drug: Leucovorin
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)

Drug: Irinotecan
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)

Drug: 5-Fluorouracil
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.




Primary Outcome Measures :
  1. The maximum dose tolerated [ Time Frame: 1 month ]
    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 :
  1. Cumulative dose of each chemotherapy drug [ Time Frame: 4 months ]
    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).

  2. Total duration of therapy [ Time Frame: 18 months ]
    To determine the total duration of therapy, which would be administered perioperatively in future studies for the curative-intent setting.

  3. Overall Response Rate [ Time Frame: 5 years ]
    To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.

  4. Progression free survival rate [ Time Frame: 5 years ]
    To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.

  5. Overall survival rate [ Time Frame: 5 years ]
    To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04361708


Contacts
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Contact: Daniel Catenacci, MD 773-702-7596 dcatenacci@medicine.bsd.uchicago.edu

Locations
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United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
Contact: Daniel Catenacci, MD    773-702-7596    dcatenacci@medicine.bsd.uchicago.edu   
Principal Investigator: Daniel Catenacci, MD         
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Daniel Catenacci, MD University of Chicago Medicine
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT04361708    
Other Study ID Numbers: IRB19-1292
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Docetaxel
Fluorouracil
Oxaliplatin
Irinotecan
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances