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

Not Applicable

Completed

• Conditions: Diarrhea; Malignant Tumor
• Interventions: Drug: Xiao Chai Hu Tang (XCHT); Other: Raloxifene; Drug: FOLFIRI regimen

• Registration Number: NCT04926545
• Lead Sponsor: Guangzhou University of Traditional Chinese Medicine

Brief 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).

Study Timeline

• Study First Submitted: 2021-05-30
• Study First Submitted QC: 2021-06-08
• Study First Posted: 2021-06-15
• Study Start: 2021-07-16
• Status Verified: 2024-04
• Primary Completion: 2024-07-20
• Study Completion: 2024-07-20
• Last Update Submitted: 2024-07-26
• Last Update Posted: 2024-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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 has previously received radiotherapy on the abdominal cavity and pelvic cavity;
5. Pregnant or lactating women;
6. Patient previously had or is now having thromboembolic (blood clotting) events.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Irinotecan naive cohort	FOLFIRI regimen	This cohort will enroll 6 postmenopausal female patients who have never received irinotecan treatment before. Patients in irinotecan naive cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 4 rounds of pharmacokinetic studies will be conducted. Round 0 (before chemotherapy): pharmacokinetic testing (raloxifene 60mg as probe) before XCHT administration, then XCHT for 4 days with pharmacokinetic testing (raloxifene 60mg as probe) on the 4th day of XCHT administration. Round 1(1st cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (without raloxifene) on day 4. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.
Irinotecan used cohort	Raloxifene	This cohort will recruit 18 patients who were treated with irinotecan previously and have at least one diarrhea episode with a severity of more than grade 2. Patients in irinotecan used cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 3 rounds of pharmacokinetic studies will be conducted. Round 1(1st cycle of chemotherapy): FOLFIRI, with pharmacokinetic testing (raloxifene 60mg as probe) on the first day of chemotherapy. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 4. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.
Irinotecan used cohort	Xiao Chai Hu Tang (XCHT)	This cohort will recruit 18 patients who were treated with irinotecan previously and have at least one diarrhea episode with a severity of more than grade 2. Patients in irinotecan used cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 3 rounds of pharmacokinetic studies will be conducted. Round 1(1st cycle of chemotherapy): FOLFIRI, with pharmacokinetic testing (raloxifene 60mg as probe) on the first day of chemotherapy. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 4. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.
Irinotecan naive cohort	Xiao Chai Hu Tang (XCHT)	This cohort will enroll 6 postmenopausal female patients who have never received irinotecan treatment before. Patients in irinotecan naive cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 4 rounds of pharmacokinetic studies will be conducted. Round 0 (before chemotherapy): pharmacokinetic testing (raloxifene 60mg as probe) before XCHT administration, then XCHT for 4 days with pharmacokinetic testing (raloxifene 60mg as probe) on the 4th day of XCHT administration. Round 1(1st cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (without raloxifene) on day 4. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.
Irinotecan naive cohort	Raloxifene	This cohort will enroll 6 postmenopausal female patients who have never received irinotecan treatment before. Patients in irinotecan naive cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 4 rounds of pharmacokinetic studies will be conducted. Round 0 (before chemotherapy): pharmacokinetic testing (raloxifene 60mg as probe) before XCHT administration, then XCHT for 4 days with pharmacokinetic testing (raloxifene 60mg as probe) on the 4th day of XCHT administration. Round 1(1st cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (without raloxifene) on day 4. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.
Irinotecan used cohort	FOLFIRI regimen	This cohort will recruit 18 patients who were treated with irinotecan previously and have at least one diarrhea episode with a severity of more than grade 2. Patients in irinotecan used cohort will receive 3 cycles of FOLFIRI chemotherapy, during which 3 rounds of pharmacokinetic studies will be conducted. Round 1(1st cycle of chemotherapy): FOLFIRI, with pharmacokinetic testing (raloxifene 60mg as probe) on the first day of chemotherapy. Round 2 (2nd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 4. Round 3 (3rd cycle of chemotherapy): XCHT for 5 days and FOLFIRI on day 4, with pharmacokinetic testing (raloxifene 60mg as probe) on day 3.

Primary Outcome Measures

Name	Time	Method
Average trajectory of irinotecan, raloxifene, XCHT and their metabolites (14 compounds)	The blood samples (2.0 ml) will be collected at 8 points for each Round (hour 0, hour 0.5, hour 1, hour 2, hour 4, hour 6, hour 8, and hour 24 after raloxifene administration)	Plasma concentration for each compounds will be tested at 8 points for each Round.

Secondary Outcome Measures

Name	Time	Method
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.
incidences of grade ≥3 diarrhea	Through study completion, an average of 2 months	The diarrhea severity will be evaluated following standard criteria in NCI-CTC AE 5.0
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
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.

Trial Locations

Locations (1)

Guangdong Provincial Hospital of Chinese Medicine; 🇨🇳 Guangzhou, Guangdong, China