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

Primary Purpose

Colorectal Neoplasms

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
TS-1, oxaliplatin
Sponsored by
Samsung Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasms focused on measuring TS-1 and oxaliplatin, Phase I/II study, Colorectal cancer, First line treatment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Samsung Medical Center

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 17, 2007
Last Updated
June 29, 2009
Sponsor
Samsung Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00531245
Brief Title
A Phase I/II Trial of TS-1 and Oxaliplatin in Patients With Advanced Colorectal Cancer
Official Title
A Phase I/II Trial of TS-1 and Oxaliplatin in Patients With Advanced Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2007
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Samsung Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Subjects meeting all of the following criteria will be considered for enrolment into the study. 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 with a diameter >20 mm using conventional CT or MRI scans or >10 mm 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 ≥ 3 months Written informed consent

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
Keywords
TS-1 and oxaliplatin, Phase I/II study, Colorectal cancer, First line treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
77 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
TS-1, oxaliplatin
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Time Frame
one year
Secondary Outcome Measure Information:
Title
To investigate the time to progression(TTP), overall survival and toxicity
Time Frame
two year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Young Suk Park, M.D., Ph.D.
Organizational Affiliation
Samsung Medical Center, Seoul, KOREA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
Citation
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
Results Reference
background
PubMed Identifier
15169795
Citation
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.
Results Reference
result
PubMed Identifier
15160338
Citation
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.
Results Reference
result
PubMed Identifier
15289858
Citation
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.
Results Reference
result

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

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