S-1, Oxaliplatin, and Irinotecan for Advanced Gastrointestinal Cancer

Dose Finding Study of S-1, Oxaliplatin, and Irinotecan Combination Chemotherapy for Patients With Inoperable Advanced or Metastatic Gastrointestinal Cancers

This study will attempt to determine the feasibility of combination of Oxaliplatin, Irinotecan, and S-1, the maximum tolerated dose and the recommended doses of the agents used, and to preliminarily evaluate the antitumor activity in untreated patients with advanced gastrointestinal cancer.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Neoplasms
• Intervention / Treatment: Drug: OIS (Oxaliplatin, Irinotecan, S-1)

Detailed Description

Oxaliplatin or irinotecan has shown a considerable anti-tumor activity, when used in combination with 5-fluorouracil (5-FU) in patients with gastrointestinal (GI) cancer. Oxaliplatin, irinotecan, and 5-FU have different mechanisms of actions and do not share the toxicity profiles. Since they have a synergistic effect, many clinical trials have been conducted recently to evaluate the efficacy of triplet combination consisting of oxaliplatin, irinotecan, and 5-FU, and demonstrated that the triple combination regimen was effective and resulted in survival benefits with favorable toxicity profiles.

S-1 and capecitabine are novel oral fluoropyrimidines and different phase III trials have shown that these oral agents are at least as active and effective as 5-FU with a superior safety profile.

Biweekly triple combination of S-1 with oxaliplatin and irinotecan (OIS) is an interesting alternative to increase convenience and to simply the treatment delivery.

In the present study, we attempt to determine the feasibility of OIS combination, the maximum tolerated dose and the recommended doses of the agents used, and to preliminarily evaluate the antitumor activity in untreated patients with advanced gastrointestinal cancer.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Anyang, Korea, Republic of
    • Hallym University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven recurrent or metastatic adenocarcinoma of the gastrointestinal tract
• Minimum age of 18 years
• ECOG Performance status 0-2
• Life expectancy >3 months
• Presence of measurable or evaluable disease by RECIST
• Prior adjuvant chemotherapy without S-1, oxaliplatin and irinotecan is allowed if more than 4 weeks elapsed since completion of chemotherapy.
• More than 4 weeks since completion of prior radiotherapy (measurable or evaluable lesions should be outside the radiation field)
• Adequate organ functions
• Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion Criteria:

• Patients treated previously with S-1, oxaliplatin, or irinotecan as adjuvant chemotherapy.
• Patients with CNS metastases or carcinomatous leptomeningitis or neurologic disease.
• Patients with active infection, severe heart disease, uncontrollable hypertension or diabetes mellitus, myocardial infarction during the preceding 6 months, pregnancy, or breast feeding
• Any previous or concurrent malignancy other than non-melanoma skin cancer or in situ cancer of uterine cervix

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: OIS (Oxaliplatin, Irinotecan, S-1); Dose level 1 treatment will be delivered as a 2-week cycle as bellows; Oxaliplatin 85 mg/m²IV on day 1; Irinotecan 120 mg/m² IV on day 1; S-1 60 mg/m2/day PO on day 1-7 Dose escalation will be continued until more than one-third of the patients in a given cohort show dose limiting toxicities (DLT) during treatment cycle 1. If at least 2 patients are observed to have DLT, this dose level is defined as the maximum tolerated dose (MTD). If exactly 1 of the 3 patients treated show DLT, 3 additional patients are treated at the current dose level.

Drug: OIS (Oxaliplatin, Irinotecan, S-1); Dose level 1 treatment will be delivered as a 2-week cycle as bellows; Oxaliplatin 85 mg/m²IV on day 1; Irinotecan 120 mg/m² IV on day 1; S-1 60 mg/m2/day PO on day 1-7 Dose escalation will be continued until more than one-third of the patients in a given cohort show dose limiting toxicities (DLT) during treatment cycle 1. If at least 2 patients are observed to have DLT, this dose level is defined as the maximum tolerated dose (MTD). If exactly 1 of the 3 patients treated show DLT, 3 additional patients are treated at the current dose level.; Other Names: Campto; TS-1; Kabioxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
maximum tolerated dose	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
progression free survival	6 months
overall survival	6 months
toxicity profiles	6 months
overall response rate	6 months
disease control rate	6 months

Collaborators and Investigators

• Sponsor: Hallym University Medical Center
• Collaborators: Pfizer; HK inno.N Corporation; Handok Inc.; Jeil Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: September 20, 2012
• First Submitted That Met QC Criteria: September 22, 2012
• First Posted (Estimate): September 26, 2012

Study Record Updates

• Last Update Posted (Estimate): February 19, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: S-1; Irinotecan; Oxaliplatin; Gastrointestinal neoplasms
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Oxaliplatin; Irinotecan
• Other Study ID Numbers: HMC-HO-GI-1203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED