Study of Simmitecan Hydrochloride in the Treatment of Advanced Solid Tumor

Study Overview
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Brief Summary
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RATIONAL: Simmitecan is an anticancer ester prodrug, which involves activation to chimmitecan. Chimmitecan，a novel CPT derivative, exhibited potent antitumor activities both in vitro and in vivo by inhibiting topoisomerase I. Also exerted comparable effects on topoisomerase I compared with topotecan and SN38 and possessed improved anticancer potency and pharmacologic profiles, compared with the clinically available CPT analogues. PURPOSE: to determine the maximum tolerated dose, the safety profile and pharmacokinetics of Simmitecan.

Official Title
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Phase I Study of Simmitecan Hydrochloride for Injection in Patients With Advanced Solid Tumor：Tolerability and Pharmacokinetics

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Simmitecan Hydrochloride for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory to standard therapy or no standard therapy available. At least one measurable lesion. Age = 18 65 years. ECOG=0-1. Life expectancy ≥ 12 weeks. More than 4 weeks after operation, chemotherapy, radiotherapy, cytotoxic agents or tyrosine kinase inhibitors. Adequate organ function: Haemoglobin ≥ 100 g/L, Absolute neutrophil count [ANC] ≥ 2×109/L,Platelets ≥ 100 × 109/L), Serum bilirubin ≤ 1.0×ULN, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5×ULN (If liver metastases, serum transaminase ≤ 2.5×ULN), Creatinine clearance ≥ 50 mL/min , LVEF ≤ 50%, QT interval (corrected by Fridericia): male < 450 ms, female < 470 ms Female: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test article. Child bearing potential, a negative urine or serum pregnancy test result before initiating Famitinib. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test article. Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. Exclusion Criteria: Less than 4 weeks from the last clinical trial. Known Spinal Cord compression or diseases of brain or pia mater by CT /MRI screening. Patients had ever severe diarrhea with prior therapy of camptothecin drugs. Concurrent severe or uncontrolled medical disease (serious infection, serious diabetes) Significant cardiovascular disease or condition including ≥ class II cardiac function (NYHA) Acute and chronic viral hepatitis. (If HBsAg +, HBV-DNA quantification ≤ LLN.) Pregnant, lactation period or men/women ready to birth. Psychiatric disorder or altered mental status. Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simmitecan Hydrochloride for Injection<br>Dissolving in 2ml water for injection, then transfering to 500 mL of 5% dextrose for i.v.90 minutes | Drug: Simmitecan Hydrochloride for Injection<br>* Either at 12.5 mg, 25 mg、50 mg、80 mg、120 mg、160 mg、200 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) | To evaluate the DLT and MTD in patients with advanced solid tumor | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Assessment | To investigate pharmacokinetics of Simmitecan and Chimmitecan:AUC,Cmax,T1/2, CL/F. | 1-4 days | 
| Efficacy Assessments | Objective Response Rate (ORR), Disease Control Rate(DCR) | 0-6 weeks | 
| Pharmacodynamic Assessments | Evaluate the genotyping of UGT1A1*6 and UGT1A1*28. | 0 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolerability, Pharmacokinetics