To Determine the MTD and to Evaluate the Safety, Efficacy and PK Profiles of TSB-9-W1 in Pre-treated Patients With mCRC. — TSB-9-W1  

Metastatic Colorectal Cancer Clinical Trial

Official title: A Phase I Study to Determine the Maximum Tolerated Dose (MTD) and to Evaluate the Safety, Efficacy and Pharmacokinetics Profiles of TSB-9-W1 in Pre-treated Patients With Metastatic Colorectal Cancer (mCRC).

Status Completed

Clinical Trial Summary

TSB-9-W1, prepared by Taiwan Sunpan Biotechnology Co., Ltd. (TSB) is a botanical drug and applied patent in the United States (US patent No. 7,138,428 B2), Japan (Patent No.

5441947) and Taiwan (Patent No. I432191 and I282280). The R&D laboratory in TSB is ISO/IEC 17025 certified by Taiwan Accreditation Foundation (TAF) and the laboratory number is 2026.The trade name of TSB-9-W1 is "IDS" in English, the registration number is 01472800 at 2011 by Intellectual Property Office (IPO), Taiwan.

A phase I and pk study to determine the Maximum Tolerated Dose (MTD) and to evaluate the safety and efficacy profiles of TSB-9-W1 in pre-treated patients with metastatic colorectal cancer (mCRC).

there are 5 cohorts and a minimal 2 patients and up to 30 patients are required at phase I.

This is a single arm study. All eligible patients with mCRC will receive TSB-9-W1 treatment.

Each treatment cycle is composed by a contiguous 2-day oral administration and a contiguous 3-day rest. Patient should take the study drug once daily before meal with approximately 250 ml or appropriate amount of water.

Clinical Trial Description

Study Design

This study is to establish the MTD of TSB-9-W1 for mCRC patients with a traditional 3+3 dose escalation method.

Study Structure

A dose escalation scenario is designed to determine the MTD according to the DLT.

Dose escalation scale:

The dose levels of investigation product are planned to be administered for determining MTD and DLT.

Dose escalation scenario:

Patients will be enrolled in a cohort of 3 patients for each dose level. Dose escalation will proceed sequentially from the lowest dose cohort. No intra-subject dose escalation is allowed. Each patient's first dose will be at least 3-day apart from the very next patient's first dose.

DLT (except diarrhea) is determined by (NCI-CTCAE) version 4.03 (2010/6/14) defined treatment related toxicity ≥ grade 3 and is worsen from the baseline. Any grade ≥ 3 toxicity (except for diarrhea) is considered a DLT unless there is a clear alternative explanation as to the attribution of the adverse event. Diarrhea event is considered as a DLT if the episode is with NCI-CTCAE Grade of 3 and this event lasts > 3 days despite appropriate supportive cares or if it is a Grade 4 event. Diarrhea event reaches Grade 4 will trigger the patient to withdraw from the study. AEs are evaluated according to the NCI-CTCAE version 4.03 as determined by the investigator to be at least possibly related in causality to the IP administration.

DLT is to be observed during the first 6-treatment cycles (1 cycle = 5 days). If none of the first 3 patients experience DLT, then dose escalation will proceed for the next cohort of patients unless the present dose level is level 5 (1000 mg/day). If 1 of 3 patients develops DLT, the cohort will be expanded to 6 patients (another 3 patients to be added subsequently). If no more than 1 of the 6 patients experiences DLT, then escalation to the next dose level will proceed unless the present dose level is level 5. If more than 1 patient develops DLT in any dose cohort, the dose escalation will be withheld and the prior dose level is considered as the MTD unless present dose level is level 1 (200 mg/day).

Data and Safety Monitoring Board (DSMB) meeting will be held to review safety data prior to each dose escalation

Cut-off criteria Enrolled patients will be treated until disease progression. This study will be ended while either condition below is confirmed.

1. All patients are Disease Progression (PD) or death or loss of follow up.

2. Last treated patient receives 9-month treatment.

Duration of Treatment

TSB-9-W1 in a 5-day treatment cycle until disease progression or study cut-off.

Compensation/reward information

There is no Compensation/reward for subject attend the study.

Results

Primary Endpoint:

MTD and DLTs DCR assessed by RECIST 1.1. ;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

• NCT number: NCT02249650
• Study type: Interventional
• Source: Taiwan Sunpan Biotechnology Development Co., Ltd.
• Status: Completed
• Phase: Phase 1
• Start date: July 10, 2017
• Completion date: August 25, 2020