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

Guangzhou University of Traditional Chinese Medicine

Status: Enrolling

Conditions: Xiao Chai Hu Tang; Irinotecan-induced Diarrhea

Treatments: Drug: Xiao Chai Hu Tang (XCHT); Drug: Placebo; Drug: Irinotecan regimen; Other: Raloxifene

Study type: Interventional

Funder types: Other

Identifiers

NCT06055179

2021KT1005-2

81961128028 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 98 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Malignant tumor confirmed by histology or cytology;

2. Age ≥ 18 years old, ≤ 75 years old;

3. ECOG score of the patient ≤ 2 points;

4. Patients who have diarrhea worse than grade 2 due to irinotecan chemotherapy (the last dose of irinotecan is administered within 1 month);

5. Patients who plan to receive 3 cycles of irinotecan chemotherapy (the dose of irinotecan ≥ 125mg/m2);

6. 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.

7. Patients who can understand and complete the questionnaires in the case report form;

8. Patients who can understand and sign the informed consent form, is well compliant, and can be followed up.

Exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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98 participants in 2 patient groups, including a placebo group

XCHT group

Experimental group

Description:

Patients will be administered with XCHT (9 g, qd, po) for 5 days each cycle of irinotecan chemotherapy for 3 cycles. The XCHT administration begins 3 days before chemotherapy in each cycle, that is the chemotherapy begins on the 4th day of XCHT 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 administration in each cycle.

Treatment:

Other: Raloxifene

Drug: Irinotecan regimen

Drug: Xiao Chai Hu Tang (XCHT)

Placebo group

Placebo Comparator group

Description:

Patients will be administered with placebo (9 g, qd, po) for 5 days each cycle of irinotecan chemotherapy for 3 cycles. The placebo administration begins 3 days before chemotherapy in each cycle, that is the chemotherapy begins on the 4th day of 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 placebo administration in each cycle.

Treatment:

Other: Raloxifene

Drug: Irinotecan regimen

Drug: Placebo