Mechanistic and Pharmacokinetic Studies of Classical Chinese Formula Xiao Chai Hu Tang Against Irinotecan-Induced Gut Toxicities(Clinical Study Part:Run-in Safety Study)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Average trajectory of irinotecan, raloxifene, XCHT and their metabolites (14 compounds)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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 has previously received radiotherapy on the abdominal cavity and pelvic cavity;
- •Pregnant or lactating women;
- •Patient previously had or is now having thromboembolic (blood clotting) events.
研究组 & 干预措施
Irinotecan naive cohort
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.
干预措施: Xiao Chai Hu Tang (XCHT) (Drug)
Irinotecan naive cohort
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.
干预措施: Raloxifene (Other)
Irinotecan naive cohort
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.
干预措施: FOLFIRI regimen (Drug)
Irinotecan used cohort
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.
干预措施: Xiao Chai Hu Tang (XCHT) (Drug)
Irinotecan used cohort
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.
干预措施: Raloxifene (Other)
Irinotecan used cohort
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.
干预措施: FOLFIRI regimen (Drug)
结局指标
主要结局
Average trajectory of irinotecan, raloxifene, XCHT and their metabolites (14 compounds)
时间窗: 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.
次要结局
- incidences of grade ≥3 diarrhea(Through study completion, an average of 2 months)
- incidence of other chemo-related adverse effects(Through study completion, an average of 2 months.)
- occult blood test for stool(Through study completion, an average of 2 months)
- incidence of diarrhea (grade ≥2)(Through study completion, an average of 2 months.)