A Phase I/II Trial of TS-1 and Oxaliplatin in Patients With Advanced Colorectal Cancer

NCT00531245 | Completed Phase 1 DMC

• 1 other identifier: 2006-01-024
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

Capecitabine and oxaliplatin(XELOX) is active first-line therapy for patients with metastatic colorectal cancer. Phase II study of TS-1, a novel oral fluoropyrimidine derivative, showed activity in patients with metastatic colorectal carcinoma. Preclinical data of TS-1 with oxaliplatin showed synergistic activity in vivo human colorectal cancer xenograft. There is no data about the optimal dose of TS-1 with 2 weeks schedule combined with oxaliplatin. Therefore in a phase I study, we would like to determine the maximum tolerated dose(MTD) of TS-1 and oxaliplatin and define the recommended dose for subsequent phase II study. And then, in a phase II study we would like to evaluate the efficacy(response rates) and toxicities of the new combination regimen in advanced colorectal cancer.

Conditions

Colorectal Neoplasms

Keywords

TS-1 and oxaliplatin; Phase I/II study; Colorectal cancer; First line treatment

Outcome Measures

Primary Outcomes (1)

• In a phase I study, to determine the maximum tolerated dose(MTD) In a phase II study, to evaluate the efficacy(response rates) and toxicities

  one year

Secondary Outcomes (1)

• To investigate the time to progression(TTP), overall survival and toxicity

  two year

Interventions

TS-1, oxaliplatin DRUG

Oxaliplatin(130 mg/m2) day 1, intravenously TS-1 at a dose of 60, 70, 80, 90, 100, 110, 120 mg/m2 given orally starting day 1 until day 14(2 weeks ON, 1 weeks OFF), every 3 weeks

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented colorectal adenocarcinoma
• Previous chemotherapy up to two regimens(including adjuvant chemotherapy and first-line chemotherapy without oxaliplatin) is allowed in phase I portion; patients are required to have discontinued chemotherapy and/or radiotherapy for at least 4weeks before entry into phase I portion. No prior chemotherapy or radiotherapy allowed(adjuvant chemotherapy and/or radiotherapy would be allowed) in phase II portion
• Age 18 to 75 years old
• At least one unidimensional measurable lesion using spiral CT scans (use of spiral CT must be documented in medical records and used consistently throughout study).
• In phase I study, prior radiotherapy is permitted if it was not administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented, and provided it has been completed at least 4 weeks before study entry.
• Performance status (ECOG scale): 0-2
• Patients can take food and drugs orally
• Adequate organ functions
• Life expectancy more than 3 months
• Written informed consent

You may not qualify if:

• Tumor type other than adenocarcinoma
• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence)
• Prior chemotherapy with TS-1 and/or oxaliplatin
• Presence of CNS metastasis
• Obvious peritoneal seeding or bowel obstruction disturbing oral intake
• Evidence of serious gastrointestinal bleeding requiring transfusion
• Symptomatic peripheral neuropathy (NCI CTC v3.0 greater than Grade I)
• Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.
• Serious illness or medical conditions, as follows; uncontrolled congestive heart failure, angina pectoris, arrhythmias, or hypertension, hepatic cirrhosis, interstitial pneumonia, pulmonary adenomatosis, psychiatric disorder that may interfere with and/or protocol compliance, unstable diabetes mellitus, uncontrolled ascites or pleural effusion, active infection
• Pregnant or lactating woman
• Women of child bearing potential not using a contraceptive method
• Receiving a concomitant treatment with drugs interacting with TS-1 or oxaliplatin, as follows; flucytosine, a fluorinated pyrimidine antifungal agent, phenytoin, warfarin
• Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
• Any patients judged by the investigator to be unfit to participate in the study

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Related Publications (4)

• Naktsuka M, Saito H, et al., A new combination chemotherapy based on oral fluoropyrimidine, TS-1 combined with oxaliplatin is highly effective against colorectal cancer in vivo 97th AACR Annual Meeting, #4730, 2006

  BACKGROUND

• Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schoffski P, Sobrero A, Van Cutsem E, Diaz-Rubio E. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004 Jun 1;22(11):2084-91. doi: 10.1200/JCO.2004.11.069.

  PMID: 15169795 RESULT

• Shirao K, Ohtsu A, Takada H, Mitachi Y, Hirakawa K, Horikoshi N, Okamura T, Hirata K, Saitoh S, Isomoto H, Satoh A. Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma. Cancer. 2004 Jun 1;100(11):2355-61. doi: 10.1002/cncr.20277.

  PMID: 15160338 RESULT

• Emura T, Suzuki N, Yamaguchi M, Ohshimo H, Fukushima M. A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA. Int J Oncol. 2004 Sep;25(3):571-8.

  PMID: 15289858 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

titanium silicide; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Young Suk Park, M.D., Ph.D.

  Samsung Medical Center, Seoul, KOREA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 17, 2007
• First Posted: September 18, 2007
• Study Start: August 1, 2006
• Primary Completion: June 1, 2008
• Study Completion: March 1, 2009
• Last Updated: July 2, 2009

Record last verified: 2007-08

Locations

KR (1)