A Phase I Study of S-1 Plus Irinotecan and Oxaliplatin in Advanced Gastrointestinal Malignancy (TIROX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00506207
Recruitment Status : Unknown
Verified July 2007 by National Cancer Center, Korea.
Recruitment status was:  Active, not recruiting
First Posted : July 25, 2007
Last Update Posted : July 25, 2007
Information provided by:
National Cancer Center, Korea

Brief Summary:
This study is an open-label, single center, and a dose-escalating phase I study to determine the maximal tolerated dose and the recommended dose of S-1 combined with irinotecan/oxaliplatin in patients with unresectable or metastatic colorectal or gastric carcinoma.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasm Gastric Neoplasm Secondary Drug: S-1, Irinotecan, Oxaliplatin Phase 1

Detailed Description:

Dose level and escalating schedule are followings;

  • S-1 (level 1/2, 3/4, 5/6: 60, 70, 80 mg/m2/day) every 12-h p.o. on days 1(evening)-15 (morning)
  • Irinotecan (level 1,2/3, 4/5, 6: 120, 130, 140, 150 mg/m2) mixed in d5w or normal saline 500 ml iv over 90 min on day 1
  • Oxaliplatin 85 mg/m2 fixed dose mixed in d5w 250 ml iv infusion over 2-h on day 1

Treatment will be administered every 3 weeks. Start at dose level 1. Thereafter, dose level 2, 3, 4, 5, and 6. If dose-limiting toxicity (DLT) occurs at dose level 1, dose level at -1 will follow

Dose escalation will be continued until more than one-third of the patients in a given cohort show dose-limiting toxicity (DLT) during treatment cycle 1. At least three patients will be enrolled in each cohort. Before escalating to the next dose level, all three patients should have received at least one treatment cycle. If none of the first three treated patients develops DLT in the first cycle at a specific dose level, dose escalation will be continued. If one of the first three treated patients develops DLT at any dose level, then three additional patients are to be entered on the same dose level. If only one in six patients at a given level experiences a DLT, escalation will proceed. The MTD is defined as the dose level at which at least one-third of patients experienced a DLT. The RD for the subsequent phase II study is defined as the preceding dose level before the MTD is attained. Intra-patient dose escalation will not be permitted. Treatment will be continued in the absence of disease progression or unacceptable toxicity with maximum 12 cycles. For purpose of determining the MTD, only DLT occurring during the first cycle of therapy will be considered.

DLTs are defined as any of following;

  • Grade 4 neutropenia lasting at least 7 days or grade 3 or 4 neutropenia associated with fever  38.3C as single axillary temperature or 38 C for 1-h
  • Grade 4 thrombocytopenia
  • Grade 3 or 4 non-hematological toxicity except alopecia, and nausea/vomiting
  • Grade 3 or 4 nausea/vomiting not reduced to grade 1 with aggressive antiemetic support
  • Inability of the patient to take 75% of the planned chemotherapy dose during the treatment period

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I and Pharmacokinetic Study of S-1 Combined With Irinotecan and Oxaliplatin in Advanced Gastrointestinal Malignancy
Study Start Date : September 2006
Estimated Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Toxicity measured by NCICTC v.3 [ Time Frame: During treatment ]
  2. Blood level of irinotecan and S-1 and their metabolites [ Time Frame: At 1st cycle ]

Secondary Outcome Measures :
  1. Maximal response rate, progression-free survival, survival

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed unresectable or metastatic colorectal or gastric carcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Measurable disease, according to the RECIST criteria or non-measurable disease Measurable lesions
  • Previous adjuvant, palliative chemotherapy including 5-FU, oxaliplatin and irinotecan, molecular targeted therapy and/or radiotherapy is allowed
  • Adequate major organ functions
  • Patients should sign a written informed consent before study entry

Exclusion Criteria:

  • Prior history of peripheral neuropathy
  • Inadequate cardiovascular
  • Serious concurrent infection or nonmalignant illness
  • Other malignancy within the past 3 years except non-melanomatous skin cancer or carcinoma in situ of the cervix
  • Psychiatric disorder that would preclude compliance
  • Pregnant, nursing women or patients with reproductive potential without contraception
  • Patients receiving a concomitant treatment with drugs interacting with S-1 such as flucytosine, phenytoin, or warfarin et al.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00506207

Korea, Republic of
National Cancer Center Korea
Goyang, Gyeonggi, Korea, Republic of, 410-769
Sponsors and Collaborators
National Cancer Center, Korea
Principal Investigator: Kyung Hae Jung, M.D.Ph.D Identifier: NCT00506207     History of Changes
Other Study ID Numbers: NCCCTS-06-166
First Posted: July 25, 2007    Key Record Dates
Last Update Posted: July 25, 2007
Last Verified: July 2007

Keywords provided by National Cancer Center, Korea:
Gastrointestinal neoplasms
Combination chemotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Stomach Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Stomach Diseases
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action