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Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics of Simmitecan Monotherapy and Combination in Patients With Advanced Solid Tumors

Phase 1
Conditions
Advanced Solid Tumor
Advanced/Metastatic Colorectal Cancer
Interventions
Registration Number
NCT02870036
Lead Sponsor
Haihe Biopharma Co., Ltd.
Brief Summary

This study evaluates the safety, tolerability, preliminary efficacy and pharmacokinetics of Simmitecan in patients with advanced solid tumors and Simmitecan, 5-fluorouracil and Leucovorin Calcium,thalidomide in patients with advanced solid tumor or advanced/metastatic colorectal cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
243
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pharmacokinetic data investigation of SimmitecanSimmitecanTo further determine the pharmacokinetic (PK) characteristics of Simmitecan monotherapy in patients with advanced solid tumors
Dose escalation study of Simmitecan combined therapySimmitecanTo determine the maximum tolerated dose (MTD) of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced solid tumor
Dose escalation study of Simmitecan combined therapy5-fluorouracil and Leucovorin CalciumTo determine the maximum tolerated dose (MTD) of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced solid tumor
Dose extension study of Simmitecan monotherapySimmitecanTo preliminarily evaluate the anti-tumor activity of Simmitecan monotherapy in patients with advanced solid tumors, and to determine the recommended phase II dose (RP2D)
Dose extension study of Simmitecan combined ThalidomideSimmitecanTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced/metastatic colorectal cancer (CRC), and to determine RP2D
Dose escalation&extension Simmitecan combined ThalidomideSimmitecanTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with gastrointestinal tumors, and to determine RP2D and MTD
Dose extension study of Simmitecan combined therapySimmitecanTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with specific tumors
Dose extension study of Simmitecan combined therapy5-fluorouracil and Leucovorin CalciumTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with specific tumors
Dose extension study of Simmitecan combined ThalidomideThalidomideTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with 5-fluorouracil/Leucovorin Calcium in patients with advanced/metastatic colorectal cancer (CRC), and to determine RP2D
Dose escalation&extension Simmitecan combined ThalidomideThalidomideTo preliminarily evaluate the anti-tumor activity of Simmitecan combined with thalidomide in patients with gastrointestinal tumors, and to determine RP2D and MTD
Primary Outcome Measures
NameTimeMethod
Cmax (maximum plasma concentration)before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
Tmax (time to maximum plasma concentration)before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
AUC (area under the plasma concentration-time curve)before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
CL (systemic clearance)before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
Vz (apparent volume of distribution)before administration (within 5 minutes before administration), 45 and 90 minutes after the start of the infusion of Simmitecan and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 hours after the completion of infusion of Simmitecan
Adverse events (AE)AEs will be classified by type, incidence, severity (graded per NCI-CTCAE [version 4.03]), time to onset, seriousness and relationship
Secondary Outcome Measures
NameTimeMethod
Objective response rate (ORR)Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

progression free survival (PFS)Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

CBR (clinical benefit rate)Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

DCR (disease control rate)Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

OS (overall survival)Imaging examination will be performed for tumor assessment every 6 weeks (±7 days) from the first dose of Simmitecan until PD, intolerable toxicity, withdrawal of consent or death.

Tumor will be evaluated according to RECIST-1.1. CT or MRI can be used for tumor imaging at the investigator's discretion.

accumulative excretion rateAccumulative excretion rate within 0-72 h after the first administration of Simmitecan.

Trial Locations

Locations (9)

Beijing Cancer Hospital

🇨🇳

Beijin, Beijing, China

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

Jiangsu Cancer Hospital

🇨🇳

Nanjing, Jiangsu, China

The Second Affiliated hospital of Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Tianjin Cancer Hospital

🇨🇳

Tianjin, Tianjin, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

The first hospital of China Medical University

🇨🇳

Shenyang, Liaoning, China

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