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

NCT06055179 | Recruiting DMC

• 2 other identifiers: 2021KT1005-281961128028
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Xiao Chai Hu Tang; Irinotecan-induced Diarrhea

Keywords

Malignant tumor; Irinotecan-induced diarrhea; Xiao Chai Hu Tang; Classical Chinese Formula; pharmacokinetic mechanism

Outcome Measures

Primary Outcomes (1)

• Incidence of diarrhea (grade ≥2)

  The diarrhea severity will be evaluated following standard criteria in NCI-CTC AE 5.0 Grade 2 is defined as Stool is increased by 4-6 times each day relative to baseline; discharge from stoma moderately increased.

  Through study completion, an average of 2 months

Secondary Outcomes (6)

• Incidence of diarrhea (grade ≥3)

  Through study completion, an average of 2 months

• Incidence of other chemo-related adverse effects

  Through study completion, an average of 2 months

• Occult blood test for stool

  Through study completion, an average of 2 months

• PK parameters(Cmax)

  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)

  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)

Study Arms (2)

XCHT group

EXPERIMENTAL

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.

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

Placebo group

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Irinotecan regimen; Other: Raloxifene

Interventions

Xiao Chai Hu Tang (XCHT) DRUG

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

Also known as: Xiao Chai Hu Tang granules from Nin Jiom Medicine Manufactory (Hong Kong) Ltd

XCHT group

Placebo DRUG

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

Also known as: Placebo provided by Nin Jiom Medicine Manufactory (Hong Kong) Ltd

Placebo group

Irinotecan regimen 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.

Placebo group; XCHT group

Raloxifene OTHER

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

Placebo group; XCHT group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou University of Traditional Chinese Medicine: lead
• University of Houston: collaborator

Study Sites (1)

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

shosaiko-to; Long-Term Synaptic Depression; Raloxifene Hydrochloride

Intervention Hierarchy (Ancestors)

Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Haibo Zhang, Prof.

  Guangdong Provincial Hospital of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanjuan Zhu, Dr.

CONTACT

86 20 81887233; zyjsophy@gzucm.edu.cn

Yadong Chen, Dr.

CONTACT

86 20 81887233; chenyadong@gzucm.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomly assigned to XCHT/placebo groups, at a 1:1 ratio, using a central randomization system provided by the TCM clinical study methodology group of Guangdong Provincial Hospital of Chinese Medicine. This group is also responsible for blinding, including keeping the blinding codes, supervision, and quality control of blinding, by allocating drug codes for each patient. Investigators will dispense the drug according to the drug codes. The investigators, the study subjects, the care givers, and the outcome assessors will be blinded to the assigned group of subjects.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2023
• First Posted: September 26, 2023
• Study Start: March 8, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 1, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)