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

NCT02249650 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SUNTSBA20110201
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; TSB-9-W1

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  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).

  up to 3 years

• Dose limiting toxicities (DLTs)

  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.

  30 days

Study Arms (1)

TSB-9-W1 cohort

EXPERIMENTAL

TSB-9-W1 200 mg/day (Cohort 1) TSB-9-W1 400 mg/day (Cohort 2) TSB-9-W1 600 mg/day (Cohort 3) TSB-9-W1 800 mg/day (Cohort 4) TSB-9-W1 1000 mg/day (Cohort 5)

Drug: TSB-9-W1

Interventions

TSB-9-W1 DRUG

Product name: TSB-9-W1 Unit dose: 100 mg per capsule Dosage form: Capsule Treatment cycle: A treatment cycle consists of 2-day on-dose oral administering and followed by a 3-day off-dose.

Also known as: TSB-9-W1(IDS)

TSB-9-W1 cohort

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male, age ≥ 20 years old
• Patient who is eligible and able to participate in the study and accepts to enter the study by signing written informed consent
• Patient has histologically or cytologically confirmed colorectal adenocarcinoma in stage IV under the Tumor-Node-Metastasis (TNM) staging system
• Patient must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Patient should have received at least two prior therapies for colorectal cancer (CRC) including oxaliplatin and irinotecan based regimens.
• Patient should have received at least one of the target therapies for CRC including Cetuximab, Bevacizumab, Panitumumab, Regorafenib, and Ziv-aflibercept.
• Patient with primary major surgery needs to have elapsed ≥ 2 weeks prior to the planned first study treatment day
• Patient who has ever received chemotherapy, or immunotherapy, or biologic therapy modalities need to wash-out ≥ 2 weeks prior to the baseline visit
• Patient who has ever received radiotherapy (including chemoradiation therapy) need to end the course ≥ 2 weeks before baseline visit (palliative radiotherapy can be performed on non-study-related local lesions)
• Patient's life expectancy ≥ 3 months
• Within 4 weeks of planned first study treatment day, adequate hematopoietic functions are presented:
• Total white blood cell (WBC) ≥ 3,000 cells/mm3
• Absolute neutrophil count (ANC) ≥ 1,500 /mm3
• Hemoglobin (Hb) ≥ 9.0 g/dL
• Platelets ≥ 100,000 cells/mm3

You may not qualify if:

• Patient who has participated in other investigational studies within 4 weeks prior to the first dose of the study medications
• Patient has history of another malignancy within 5 years prior to study entry, except curatively treated non-melanoma skin cancer, or cervical cancer in situ
• Patient with known or suspected hypersensitivity to TSB-9-W1 or its formulation excipients
• Patient has another severe and/or life-threatening medical disease
• Patient has immuno-compromised condition, with known autoimmune conditions or human immunodeficiency virus (HIV) seropositivity
• Patient with active systemic infections, active and clinically significant cardiac diseases, clinically active gastroduodenal ulcers, or medical conditions that may significantly affect adequate absorption of investigational product
• Patient with known brain metastasis
• Patient with medical, social or psychological factors interfering with compliance
• Patient having grade ≥ 3 adverse event (AE) based on National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE) 4.03 except blood total bilirubin, AST, ALT, ALP and creatinine at baseline visit
• Patient having grade ≥ 1 diarrhea based on NCI-CTCAE 4.03.
• Patient with a medical history of myocardial infraction in the last 6 months

Sponsors & Collaborators

• Taiwan Sunpan Biotechnology Development Co., Ltd.: lead
• Virginia Contract Research Organization Co., Ltd.: collaborator

Study Sites (1)

Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Related Publications (2)

• Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20. doi: 10.1093/jnci/djp079. Epub 2009 May 12.

  PMID: 19436029 BACKGROUND

• Sanoff HK, Sargent DJ, Campbell ME, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Goldberg RM. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008 Dec 10;26(35):5721-7. doi: 10.1200/JCO.2008.17.7147. Epub 2008 Nov 10.

  PMID: 19001325 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Tsai-Sheng Yang, Bachelor

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 25, 2014
• Study Start: July 10, 2017
• Primary Completion: February 12, 2020
• Study Completion: August 25, 2020
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)