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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат 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)
• Препарат 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)
• Препарат 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)
• Препарат 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)
• Препарат 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.

Первичные конечные точки

• The maximum dose tolerated [Срок оценки: 1 month]

Вторичные конечные точки (5)

• Cumulative dose of each chemotherapy drug [Срок оценки: 4 months]
• Total duration of therapy [Срок оценки: 18 months]
• Overall Response Rate [Срок оценки: 5 years]
• Progression free survival rate [Срок оценки: 5 years]
• Overall survival rate [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• The University of Chicago — Chicago

Идентификаторы

NCT: NCT04361708 · IRB19-1292

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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