NCT04926545

XCHT for Irinotecan-Induced Gut Toxicities (Run-in Study)

Mechanistic and Pharmacokinetic Studies of Classical Chinese Formula Xiao Chai Hu Tang Against Irinotecan-Induced Gut Toxicities(Clinical Study Part:Run-in Safety Study)

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Guangzhou University of Traditional Chinese Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Run-in safety study, to determine the safety of co-administration of irinotecan, raloxifene, and Xiao Chai Hu Tang (XCHT), and to optimize the blood collection time points for pharmacokinetic (PK) study for another randomized control trial.

Detailed description

There will be two cohorts with a total of 24 patients in this study. Cohort A will enroll 6 naïve postmenopausal female patients who have never received irinotecan treatment before. Patients in this group will have 4 rounds of studies following different protocol to determine (1) the impact of XCHT on raloxifene PK (Round 0, co-administration of XCHT and raloxifene); (2) the impact of XCHT on irinotecan PK (Round 1, co-administration of XCHT and standard FOLFIRI); (3) the safety of co- administration of XCHT, raloxifene, and FOLFIRI and evaluation of raloxifene as a probe for XCHT treatment to prevent irinotecan-induced severe delayed-onset diarrhea (Round 2 and 3, co-administration of XCHT, raloxifene, and standard FOLFIRI). The reason to recruit postmenopausal women is that these patients usually take raloxifene to prevent osteoporosis and the risk of raloxifene is expected to be limited. Cohort B will recruit 18 patients who were treated with irinotecan previously and have at least one diarrhea episode with a severity of ≥grade 2. The reason we propose to recruit patients who had diarrhea induced by irinotecan is that these patients are supposed to be sensitive to irinotecan so that we can determine the PK changes and safety. Patients in this group will have 3 rounds of FOLFIRI chemotherapy to determine (1) the impact of FOLFIRI on raloxifene PK (Round 1, co-administration of FOLFIRI with raloxifene); (2) the complete PK profile of SN-38, SN-38G, raloxifene, raloxifene-glucuronide, and XCHT components (Round 2, co- administration of FOLFIRI with XCHT and raloxifene); and (3) the safety of co-administration of XCHT, raloxifene, and FOLFIRI in sensitive patients and evaluation of raloxifene as a probe for XCHT treatment to prevent irinotecan-induced diarrhea (Round 3, co-administration of XCHT, raloxifene and standard FOLFIRI).

Conditions

• Malignant Tumor
• Diarrhea

Interventions

Type	Name	Description
DRUG	Xiao Chai Hu Tang (XCHT)	XCHT 9g, po qd, 3 days before each cycle of chemotherapy for 5 days, except the 1st cycle of chemotherapy for irinotecan used cohort patients. Additional XCHT, 9g qd will be orally administrated for 4 days during the Round 0 study for irinotecan naive cohort patients.
OTHER	Raloxifene	Raloxifene 60mg po, used as probe for pharmacokinetic testing. For irinotecan naive cohort patients, raloxifene 60mg will be orally administrated on Day 1 and Day 5 (4th day of XCHT administration) during round 0 study, Day 3 (the day before chemotherapy) during round 2 and round 3 study. For irinotecan used cohort patients, raloxifene 60mg will be orally administrated on Day 1 (irinotecan using day) during round 1 study, Day 4 (irinotecan using day) during round 2 study, and Day 3 (the day before chemotherapy) during round 3 study.
DRUG	FOLFIRI regimen	Patients will receive 3 cycles of FOLFIRI regimen for chemotherapy. Irinotecan intravenous (IV) infusion (180 mg/m2) through a drip into the bloodstream over 90 minutes. Folinic acid (400 mg/m2) IV infusion through a drip into the bloodstream over 2 hours. 5-fluorouracil (5-FU) IV bolus (400 mg/m2) into the bloodstream over 5 minutes, followed by 5-FU (2400 mg/m2) continuous IV infusion through a drip or pump into the bloodstream for 46-48 hours.

Timeline

• Start date: 2021-07-16
• Primary completion: 2024-07-20
• Completion: 2024-07-20
• First posted: 2021-06-15
• Last updated: 2024-07-30

Locations

1 site across 1 country: China