Clinical trial NCT06055179: XCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)
Official title: Mechanistic and Pharmacokinetic Studies of Classical Chinese Formula Xiao Chai Hu Tang (XCHT) Against Irinotecan-Induced Gut Toxicities(Clinical Study Part:Randomized Controlled Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Xiao Chai Hu Tang
Irinotecan-induced Diarrhea
Keywords: Malignant tumor
Irinotecan-induced diarrhea
Xiao Chai Hu Tang
Classical Chinese Formula
pharmacokinetic mechanism
Lead sponsor: Guangzhou University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: University of Houston
First posted: 2023-09-26
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of diarrhea (grade ≥2)
timeFrame: Through study completion, an average of 2 months
Secondary outcomes:
measure: Incidence of diarrhea (grade ≥3)
timeFrame: Through study completion, an average of 2 months
measure: Incidence of other chemo-related adverse effects
timeFrame: Through study completion, an average of 2 months
measure: Occult blood test for stool
timeFrame: Through study completion, an average of 2 months
measure: PK parameters(Cmax)
timeFrame: 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)
measure: PK parameters(AUC)
timeFrame: 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)
measure: PK parameters(T1/2)
timeFrame: 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)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
Study officials:
affiliation: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: Haibo Zhang, Prof.
role: PRINCIPAL_INVESTIGATOR
References: