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

This study has been completed.
Sponsor:
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT00531245
First received: September 17, 2007
Last updated: June 29, 2009
Last verified: August 2007
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Drug: TS-1, oxaliplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of TS-1 and Oxaliplatin in Patients With Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

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 [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate the time to progression(TTP), overall survival and toxicity [ Time Frame: two year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 77
Study Start Date: August 2006
Study Completion Date: March 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: TS-1, oxaliplatin
    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
Detailed Description:

Subjects meeting all of the following criteria will be considered for enrolment into the study.

  1. Histologically documented colorectal adenocarcinoma
  2. 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
  3. Age 18 to 75 years old
  4. 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).
  5. 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.
  6. Performance status (ECOG scale): 0-2
  7. Patients can take food and drugs orally
  8. Adequate organ functions
  9. Life expectancy ≥ 3 months
  10. Written informed consent
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531245

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Young Suk Park, M.D., Ph.D. Samsung Medical Center, Seoul, KOREA
  More Information

Publications:
Responsible Party: Young Suk Park, Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT00531245     History of Changes
Other Study ID Numbers: 2006-01-024
Study First Received: September 17, 2007
Last Updated: June 29, 2009
Health Authority: Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
TS-1 and oxaliplatin
Phase I/II study
Colorectal cancer
First line treatment

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014