Clinical trial NCT04361708: Safety of Combining Irinotecan 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Adenocarcinoma
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: The maximum dose tolerated
timeFrame: 1 month
Secondary outcomes:
measure: Cumulative dose of each chemotherapy drug
timeFrame: 4 months
measure: Total duration of therapy
timeFrame: 18 months
measure: Overall Response Rate
timeFrame: 5 years
measure: Progression free survival rate
timeFrame: 5 years
measure: Overall survival rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago Medicine
name: Daniel Catenacci, MD
role: PRINCIPAL_INVESTIGATOR
References: