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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Simmitecan Hydrochloride for Injection

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • The Tumor Hospital Affiliated to Harbin Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Haihe Biopharma Co., Ltd.
• Collaborators: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
• Investigators: Principal Investigator: Aiping Zhou, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Yong Xu, M.D., West China Hospital; Principal Investigator: Qingyuan Zhang, M.D., The Tumor Hospital Affiliated to Harbin Medical University

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 8, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 16, 2013

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: December 18, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Tolerability
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LP-101