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

Phase 1

Completed

• Conditions: Gastrointestinal Neoplasms
• Interventions: Drug: OIS (Oxaliplatin, Irinotecan, S-1)

• Registration Number: NCT01693445
• Lead Sponsor: Hallym University Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2012-06
• Status Verified: 2012-09
• Study First Submitted: 2012-09-20
• Study First Submitted QC: 2012-09-22
• Study First Posted: 2012-09-26
• Primary Completion: 2014-02
• Study Completion: 2014-08
• Last Update Submitted: 2016-02-18
• Last Update Posted: 2016-02-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OIS (Oxaliplatin, Irinotecan, S-1)	OIS (Oxaliplatin, Irinotecan, S-1)	Dose level 1 treatment will be delivered as a 2-week cycle as bellows; 1. Oxaliplatin 85 mg/m²IV on day 1 2. Irinotecan 120 mg/m² IV on day 1 3. 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.

Primary Outcome Measures

Name	Time	Method
maximum tolerated dose	6 months

Secondary Outcome Measures

Name	Time	Method
toxicity profiles	6 months
overall response rate	6 months
progression free survival	6 months
overall survival	6 months
disease control rate	6 months

Trial Locations

Locations (1)

Hallym University Medical Center; 🇰🇷 Anyang, Korea, Republic of