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

NCT ID: NCT06055179

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-08
• Study Completion Date: 2026-12-01

Brief Summary

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.

Detailed 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.

Conditions

Xiao Chai Hu Tang; Irinotecan-induced Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

XCHT group

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.

Group Type: EXPERIMENTAL

Xiao Chai Hu Tang (XCHT)

Intervention Type: DRUG

XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.

Irinotecan regimen

Intervention Type: DRUG

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 regimen:irinotecan (180 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Capecitabine (1000 mg/m²) PO bid on day 1-14. Every 3 weeks.

FOLFOXIRI regimen:irinotecan (165 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Oxaliplatin (85 mg/m2) intravenous (IV) for over 2 hours on Day 1.Folinic acid (400 mg/m2) IV over 2 hours on Day 1, followed by 5-FU (2400 - 3200 mg/m2) IV continuously for 48 hours. Every 2 weeks.

Raloxifene

Intervention Type: OTHER

Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.

Placebo group

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.

Irinotecan regimen

Intervention Type: DRUG

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 regimen:irinotecan (180 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Capecitabine (1000 mg/m²) PO bid on day 1-14. Every 3 weeks.

FOLFOXIRI regimen:irinotecan (165 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Oxaliplatin (85 mg/m2) intravenous (IV) for over 2 hours on Day 1.Folinic acid (400 mg/m2) IV over 2 hours on Day 1, followed by 5-FU (2400 - 3200 mg/m2) IV continuously for 48 hours. Every 2 weeks.

Raloxifene

Intervention Type: OTHER

Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.

Interventions

Xiao Chai Hu Tang (XCHT)

XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.

Intervention Type: DRUG

Placebo

Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.

Intervention Type: DRUG

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 regimen:irinotecan (180 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Capecitabine (1000 mg/m²) PO bid on day 1-14. Every 3 weeks.

FOLFOXIRI regimen:irinotecan (165 mg/m2) intravenous (IV) for over 90 minutes on Day 1. Oxaliplatin (85 mg/m2) intravenous (IV) for over 2 hours on Day 1.Folinic acid (400 mg/m2) IV over 2 hours on Day 1, followed by 5-FU (2400 - 3200 mg/m2) IV continuously for 48 hours. Every 2 weeks.

Intervention Type: DRUG

Raloxifene

Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.

Intervention Type: OTHER

Other Intervention Names

Xiao Chai Hu Tang granules from Nin Jiom Medicine Manufactory (Hong Kong) Ltd; Placebo provided by Nin Jiom Medicine Manufactory (Hong Kong) Ltd

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Houston

OTHER

Sponsor Role: collaborator

Guangzhou University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Haibo Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Haibo Zhang, Prof.

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial Hospital of Traditional Chinese Medicine

Locations

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yanjuan Zhu, Dr.

Role: CONTACT

zyjsophy@gzucm.edu.cn

86 20 81887233 ext. 34830

Yadong Chen, Dr.

Role: CONTACT

chenyadong@gzucm.edu.cn

86 20 81887233 ext. 34830

Facility Contacts

Haibo Zhang, Prof

Role: primary

haibozh@gzucm.edu.cn

86-020-81887233 ext. 34830

Other Identifiers

81961128028

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2021KT1005-2

Identifier Type: -

Identifier Source: org_study_id