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

NCT04926545 | Completed DMC

• 2 other identifiers: 2021KT100581961128028
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Tumor; Diarrhea

Keywords

Malignant tumor; Irinotecan; chemotherapy-induced diarrhea; Classical Chinese Formula; safety

Outcome Measures

Primary Outcomes (1)

• Average trajectory of irinotecan, raloxifene, XCHT and their metabolites (14 compounds)

  Plasma concentration for each compounds will be tested at 8 points for each Round.

  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)

Secondary Outcomes (4)

• incidences of grade ≥3 diarrhea

  Through study completion, an average of 2 months

• occult blood test for stool

  Through study completion, an average of 2 months

• incidence of other chemo-related adverse effects

  Through study completion, an average of 2 months.

• incidence of diarrhea (grade ≥2)

  Through study completion, an average of 2 months.

Study Arms (2)

Irinotecan naive cohort

EXPERIMENTAL

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.

Drug: Xiao Chai Hu Tang (XCHT); Other: Raloxifene; Drug: FOLFIRI regimen

Irinotecan used cohort

EXPERIMENTAL

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.

Drug: Xiao Chai Hu Tang (XCHT); Other: Raloxifene; Drug: FOLFIRI regimen

Interventions

Xiao Chai Hu Tang (XCHT) DRUG

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.

Also known as: Xiao Chai Hu Tang granules from Nin Jiom Medicine Manufactory (Hong Kong) Ltd.

Irinotecan naive cohort; Irinotecan used cohort

Raloxifene OTHER

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.

Also known as: Evista from Eli Lilly

Irinotecan naive cohort; Irinotecan used cohort

FOLFIRI regimen DRUG

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.

Also known as: Irinotecan Hydrochloride from Pfizer+Folinic acid+5-fluorouracil (5-FU)

Irinotecan naive cohort; Irinotecan used cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Malignant tumor confirmed by histology or cytology;
• Postmenopausal women, after bilateral oophorectomy; age \> 60 years old, or age \< 60 years old with menopause for more than 1 year;
• Age ≥ 18 years old, ≤ 75 years old;
• ECOG score of the patient ≤ 2 points;
• Never been treated with irinotecan;
• Plan to receive at least 3 rounds of FOLFIRI chemotherapy determined by physicians;
• Normal organ functions can meet the requirements for systemic chemotherapy:
• Reserve functions of normal bone marrow: absolute neutrophil count (ANC) ≥ 1.5×109/L, PLT ≥ 100×109/L, hemoglobin ≥ 90 g/L;
• Normal renal functions: serum creatinine ≤ 1.5 mg/dl (133 μmol/L) and/or creatinine clearance ≥ 60 ml/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; If abnormal hepatic functions are caused by a potentially malignant tumor, and AST ＆ ALT ≤ 5 × ULN;
• Patient is willing to participate and cooperate to complete the questions in the case report form;
• Patient can understand and sign the informed consent form, is well compliant, and can be followed up.
• Cohort B: cancer patients who experienced irinotecan -induced diarrhea (grade \>2)
• Malignant tumor confirmed by histology or cytology;
• Age ≥ 18 years old, ≤ 75 years old;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou University of Traditional Chinese Medicine: lead
• University of Houston: collaborator

Study Sites (1)

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, 510120, China

Location

MeSH Terms

Conditions

Neoplasms; Diarrhea

Interventions

shosaiko-to; Long-Term Synaptic Depression; Raloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Haibo Zhang, Prof

  Guangdong Provincial Hospital of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2021
• First Posted: June 15, 2021
• Study Start: July 16, 2021
• Primary Completion: July 20, 2024
• Study Completion: July 20, 2024
• Last Updated: July 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)