Study of Simmitecan Hydrochloride in the Treatment of Advanced Solid Tumor

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01832298
• Other study ID #: LP-101
• Status: Completed
• Phase: Phase 1
• First received: April 8, 2013
• Last updated: December 18, 2016
• Start date: December 2012
• Est. completion date: August 2016

Study information

• Verified date: October 2016
• Source: ShangHai HaiHe Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: August 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• Simmitecan Hydrochloride for Injection
Either at 12.5 mg, 25 mg?50 mg?80 mg?120 mg?160 mg?200 mg

Locations

Country	Name	City	State
China	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The tumor hospital affiliated to Harbin medical university	Harbin	Heilongjiang

Sponsors (2)

Lead Sponsor	Collaborator
ShangHai HaiHe Pharmaceutical	Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)	To evaluate the DLT and MTD in patients with advanced solid tumor	2 weeks	Yes
Secondary	Pharmacokinetic Assessment	To investigate pharmacokinetics of Simmitecan and Chimmitecan:AUC,Cmax,T1/2, CL/F.	1-4 days	No
Secondary	Efficacy Assessments	Objective Response Rate (ORR), Disease Control Rate(DCR)	0-6 weeks	No
Secondary	Pharmacodynamic Assessments	Evaluate the genotyping of UGT1A1*6 and UGT1A1*28.	0 days	No