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
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
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
NCT ID
NCT00531245
First Posted
September 17, 2007
Last Updated
June 29, 2009
Sponsor
Samsung Medical Center
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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