Back to resultsXCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)
Primary Purpose
Xiao Chai Hu Tang, Irinotecan-induced Diarrhea
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Xiao Chai Hu Tang (XCHT)
Placebo
FOLFIRI/mXELIRI regimen
Raloxifene
Sponsored by
About this trial
This is an interventional prevention trial for Xiao Chai Hu Tang focused on measuring Malignant tumor, Irinotecan-induced diarrhea, Xiao Chai Hu Tang, Classical Chinese Formula, pharmacokinetic mechanism
Eligibility Criteria
Inclusion criteria: 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 FOLFIRI/mXELIRI chemotherapy; 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. Exclusion Criteria: 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.
Sites / Locations
- Guangdong Provincial Hospital of Traditional Chinese Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
XCHT group
Placebo group
Arm Description
Patients will be administered with XCHT (9 g, qd, po) for 5 days each cycle of FOLFIRI/mXELIRI 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.
Patients will be administered with placebo (9 g, qd, po) for 5 days each cycle of FOLFIRI/mXELIRI 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Incidence of diarrhea (grade ≥3)
The diarrhea severity will be evaluated following standard criteria in NCI-CTC AE 5.0
Incidence of other chemo-related adverse effects
Other adverse reactions will be evaluated following standard criteria in NCI-CTC AE 5.0
Occult blood test for stool
Occult blood test for stool, reported as negative, weak positive, and positive.
PK parameters(Cmax)
Cmax ,if with complete data, in each cycle of Cmax for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
PK parameters(AUC)
AUC 0-24hr, if with complete data, in each cycle of AUC0-24hr for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
PK parameters(T1/2)
T1/2, if with complete data, in each cycle of T1/2 for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
Full Information
NCT ID
NCT06055179
First Posted
September 9, 2023
Last Updated
October 10, 2023
Sponsor
Guangzhou University of Traditional Chinese Medicine
Collaborators
University of Houston
1. Study Identification
Unique Protocol Identification Number
NCT06055179
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Guangzhou University of Traditional Chinese Medicine
Collaborators
University of Houston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 FOLFIRI/mXELIRI 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Xiao Chai Hu Tang, Irinotecan-induced Diarrhea
Keywords
Malignant tumor, Irinotecan-induced diarrhea, Xiao Chai Hu Tang, Classical Chinese Formula, pharmacokinetic mechanism
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
98 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
XCHT group
Arm Type
Experimental
Arm Description
Patients will be administered with XCHT (9 g, qd, po) for 5 days each cycle of FOLFIRI/mXELIRI 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.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Patients will be administered with placebo (9 g, qd, po) for 5 days each cycle of FOLFIRI/mXELIRI 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.
Intervention Type
Drug
Intervention Name(s)
Xiao Chai Hu Tang (XCHT)
Other Intervention Name(s)
Xiao Chai Hu Tang granules from Nin Jiom Medicine Manufactory (Hong Kong) Ltd
Intervention Description
XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo provided by Nin Jiom Medicine Manufactory (Hong Kong) Ltd
Intervention Description
Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
Intervention Type
Drug
Intervention Name(s)
FOLFIRI/mXELIRI regimen
Intervention Description
Patients will receive 3 cycles of FOLFIRI/mXELIRI 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.
Intervention Type
Other
Intervention Name(s)
Raloxifene
Intervention Description
Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.
Primary Outcome Measure Information:
Title
Incidence of diarrhea (grade ≥2)
Description
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.
Time Frame
Through study completion, an average of 2 months
Secondary Outcome Measure Information:
Title
Incidence of diarrhea (grade ≥3)
Description
The diarrhea severity will be evaluated following standard criteria in NCI-CTC AE 5.0
Time Frame
Through study completion, an average of 2 months
Title
Incidence of other chemo-related adverse effects
Description
Other adverse reactions will be evaluated following standard criteria in NCI-CTC AE 5.0
Time Frame
Through study completion, an average of 2 months
Title
Occult blood test for stool
Description
Occult blood test for stool, reported as negative, weak positive, and positive.
Time Frame
Through study completion, an average of 2 months
Title
PK parameters(Cmax)
Description
Cmax ,if with complete data, in each cycle of Cmax for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
Time Frame
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)
Title
PK parameters(AUC)
Description
AUC 0-24hr, if with complete data, in each cycle of AUC0-24hr for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
Time Frame
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)
Title
PK parameters(T1/2)
Description
T1/2, if with complete data, in each cycle of T1/2 for XCHT and their metabolites (14 compounds) and intestinal UGT enzyme probe (raloxifene and metabolites)
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
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 FOLFIRI/mXELIRI chemotherapy;
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yanjuan Zhu, Dr.
Phone
86 20 81887233
Ext
34830
Email
zyjsophy@gzucm.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Yadong Chen, Dr.
Phone
86 20 81887233
Ext
34830
Email
chenyadong@gzucm.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haibo Zhang, Prof.
Organizational Affiliation
Guangdong Provincial Hospital of Traditional Chinese Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guangdong Provincial Hospital of Traditional Chinese Medicine
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
XCHT for Irinotecan-Induced Gut Toxicities (Randomized Controlled Trial)
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