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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
98
XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
Placebo 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, for 3 cycles of chemotherapy.
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.
Guangdong Provincial Hospital of Traditional Chinese Medicine
Guangzhou, Guangdong, China
RECRUITINGIncidence 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.
Time frame: Through study completion, an average of 2 months
Incidence of diarrhea (grade ≥3)
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
Incidence of other chemo-related adverse effects
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
Occult blood test for stool
Occult blood test for stool, reported as negative, weak positive, and positive.
Time frame: Through study completion, an average of 2 months
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)
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)
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)
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)
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Raloxifene 60mg po, used as probe for pharmacokinetic testing, on Day 3 (the day before chemotherapy), for 3 cycles of chemotherapy.
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)
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)