Study of Simmitecan Hydrochloride in the Treatment of Advanced Solid Tumor

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

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.

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