Irinotecan-induced Diarrhea, Xiao Chai Hu Tang
Conditions
Keywords
Malignant tumor, Irinotecan-induced diarrhea, Xiao Chai Hu Tang, Classical Chinese Formula, pharmacokinetic mechanism
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.
Interventions
XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
DRUGPlacebo
Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
DRUGIrinotecan 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.
OTHERRaloxifene
Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.
Sponsors
University of Houston
Guangzhou University of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of diarrhea (grade ≥2) | Through study completion, an average of 2 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of other chemo-related adverse effects | Through study completion, an average of 2 months | Other adverse reactions will be evaluated following standard criteria in NCI-CTC AE 5.0 |
| Occult blood test for stool | Through study completion, an average of 2 months | Occult blood test for stool, reported as negative, weak positive, and positive. |
| Incidence of diarrhea (grade ≥3) | Through study completion, an average of 2 months | The diarrhea severity will be evaluated following standard criteria in NCI-CTC AE 5.0 |
| 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) | 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) | 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) | 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) |
| 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) | 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) |
Countries
China
Contacts
Primary ContactYanjuan Zhu, Dr.
Backup ContactYadong Chen, Dr.
Outcome results
None listed