XCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)

Официальное название

Mechanistic and Pharmacokinetic Studies of Classical Chinese Formula Xiao Chai Hu Tang (XCHT) Against Irinotecan-Induced Gut Toxicities(Clinical Study Part:Randomized Controlled Trial)

Обзор

Randomized double-blind placebo-controlled trial (RCT) study, to determine the impact of XCHT on irinotecan-induced severe delayed-onset diarrhea (SDOD), and to determine the feasibility of using plasma raloxifene-4'-glucuronide as a probe for intestinal UGT activity.

Подробное описание

A total of 98 patients, who are planning to recieve at least 3 cycles of irinotecan chemotherapy, will be randomly assigned, at a 1:1 ratio, to XCHT group or placebo group, using a central randomization system. Patients will be administered with XCHT/placebo (9 g, qd, po) for 5 days each cycle of chemotherapy for 3 cycles. The XCHT/placebo administration begins 3 days before chemotherapy in each cycle, that is the chemotherapy begins on the 4th day of XCHT/placebo administration. Plasma will be collected for pharmacokinetic testing (using raloxifene 60mg po as probe), on the day before chemotherapy, that is on the 3rd day of XCHT/placebo administration in each cycle. The purpose of this study includes 1) to determine the safety and efficacy of XCHT for prevention of irinotecan-induced diarrhea; 2) to determine the PK profile of SN-38, SN-38G, raloxifene, raloxifene-glucuronide, and XCHT components; and 3) to validate the use of raloxifene-4'G as a probe for irinotecan-induced diarrhea.

Вмешательства

• Препарат Xiao Chai Hu Tang (XCHT)
  XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
• Препарат Placebo
  Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
• Препарат Irinotecan regimen
  Patients will receive 3 cycles of irinotecan chemotherapy. FOLFIRI regimen:irinotecan (180 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Folinic acid (400 mg/m2) IV over 2 hours on Day 1. 5-fluorouracil (5-FU) IV bolus (400 mg/m2) over 5 minutes on Day 1, followed by 5-FU (2400 mg/m2) IV continuously for 46-48 hours. Every 2 weeks. mXELIRI regimen:irinotecan (200 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Capecitabine (800 mg/m²) PO bid on day 1-14. Every 3 weeks. CapIRI reg
• Другое Raloxifene
  Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.

Первичные конечные точки

• Incidence of diarrhea (grade ≥2) [Срок оценки: Through study completion, an average of 2 months]

Вторичные конечные точки (6)

• Incidence of diarrhea (grade ≥3) [Срок оценки: Through study completion, an average of 2 months]
• Incidence of other chemo-related adverse effects [Срок оценки: Through study completion, an average of 2 months]
• Occult blood test for stool [Срок оценки: Through study completion, an average of 2 months]
• PK parameters(Cmax) [Срок оценки: The blood samples (2.0 ml) will be collected at 4 points for each cycle(hour 0, hour 1, hour 2, hour 4 after raloxifene administration)]
• PK parameters(AUC) [Срок оценки: The blood samples (2.0 ml) will be collected at 4 points for each cycle(hour 0, hour 1, hour 2, hour 4 after raloxifene administration)]
• PK parameters(T1/2) [Срок оценки: The blood samples (2.0 ml) will be collected at 4 points for each cycle(hour 0, hour 1, hour 2, hour 4 after raloxifene administration)]

Критерии участия

Критерии включения

• Malignant tumor confirmed by histology or cytology;
• Age ≥ 18 years old, ≤ 75 years old;
• ECOG score of the patient ≤ 2 points;
• Patients who have diarrhea worse than grade 2 due to irinotecan chemotherapy (the last dose of irinotecan is administered within 1 month);
• Patients who plan to receive 3 cycles of irinotecan chemotherapy (the dose of irinotecan ≥ 125mg/m2);
• Normal organ functions which can meet the requirements for systemic chemotherapy:

• Normal bone marrow function: absolute neutrophil count (ANC) ≥ 1.5×109/L, PLT ≥ 100×109/L, hemoglobin ≥ 90g/L;
• Normal renal functions: serum creatinine ≤ 1.5mg/dl (133μmol/L) and/or creatinine clearance ≥ 60ml/min;
• Normal hepatic functions: total serum bilirubin level ≤ 1.5 times of the upper limit of normal value (ULN), serum aspartate aminotransferase (AST) \& alanine aminotransferase (ALT) ≤ 2.5× ULN; AST \& ALT ≤ 5 × ULN if abnormal hepatic functions are caused by a potentially malignant tumor.
• Patients who can understand and complete the questionnaires in the case report form;
• Patients who can understand and sign the informed consent form, is well compliant, and can be followed up.

Критерии исключения

• Patients with diagnosed depression, obsession or/and schizophrenia;
• Patients with diagnosed inflammatory bowel diseases (including Crohn's disease, ulcerative colitis)
• Patient with active tuberculosis and other uncontrolled infections;
• Patient who has previously received radiotherapy on the abdominal cavity or pelvic cavity;
• Pregnant or lactating women;
• Patient who previously had or is now having thromboembolic events.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Guangdong Provincial Hospital of Traditional Chinese Medicine — Гуанчжоу

Идентификаторы

NCT: NCT06055179 · 2021KT1005-2 · 81961128028

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗