A Phase I/II Trial of Docetaxel and Oxaliplatin in Patients With Advanced Gastric Cancer

Study Overview
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Brief Summary
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Gastric cancer is the most common malignancy in Korea. The prognosis of unresectable gastric cancer has been improved by cytotoxic chemotherapy, but median survival rarely exceeds 1 year. New agents such as taxane, irinotecan and oxaliplatin combined with old agents such as 5-FU with or without leucovorin, doxorubicin, cisplatin showed higher response rates in phase II studies. Docetaxel as a single agents showed response rates of 17-24%, and the combination of docetaxel and cisplatin has shown a response rate of 37-56% and overall survival of 9-10.4 months. Oxaliplatin in combination with 5-FU and leucovorin(FOLFOX-6) showed an objective response rate of 50%, which included a 4% complete response. The preclinical studies, oxaliplatin has shown additive or synergistic cytotoxic properties with fluoropyrimidines, thymidylate synthase inhibitors, topoisomerase I inhibitors, microtubule inhibitors and DNA modifying/alkylating agents. The combination of docetaxel and oxaliplatin has been studied previously in the phase I setting in patients with metastatic breast and non-small cell lung cancer. The combination of docetaxel and oxaliplatin is a feasible and well tolerated regimen. Recommended doses were 75mg/m2 for docetaxel on day 1 and 70mg/m2 for oxaliplatin on day 2 without G-CSF support. The aim of this trial is to determine the dose limiting toxicities, maximum tolerated dose(MTD) and efficacy of oxaliplatin and docetaxel as combination chemotherapy in patients with advanced gastric cancer.

Detailed Description
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Primary objectives : To define the dose-limiting toxicity and maximum tolerated dose in phase I study To evaluate the overall response rate in phase II study Secondary objectives : To evaluate the safety and tolerability of the treatment combination. To estimate overall survival. To estimate the time to progression and the duration of overall response.

Official Title
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A Phase I/II Trial of Docetaxel and Oxaliplatin in Patients With Advanced Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: docetaxel, oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction 18 ≤ age ≤ 70 ECOG performance status of 0 - 2 At least one definite measurable lesion(s): ≥ 1 cm on spiral CT scan or ≥ 2 cm in physical examination Previously untreated metastatic gastric cancer patients or relapsed gastric cancer patients (patients with recurrence at least 6 months from the date of last administration of adjuvant chemotherapy and/or radiation therapy with 5-FU and/or leucovorin containing regimen will be included in the study) Written informed consent Minimum life expectancy of 12 weeks Adequate liver, renal, bone marrow functions as evidence by the following; Absolute neutrophil count > 1.5 x 109/L; platelets > 100 x 109/L; ASAT and/or ALAT < 3 UNL; serum creatinine ≤ 1.5 ULN Exclusion Criteria: Any other malignancies within the past 5 years except skin basal cell cancer or CIS of cervix Serious comorbid diseases Pregnancy or lactation Previous history of drug allergy to one of the drugs in the study regimen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: docetaxel, oxaliplatin|Oxaliplatin will be administered in combination with docetaxel as a first-line chemotherapy in advanced gastric cancer patients. Each cycle is repeated every 3 weeks. Docetaxel Oxaliplatin Level 1 60 mg/m2/day 1 100 mg/m2/day 1 Level 2 75 mg/m2/day 1 100 mg/m2/day 1 Level 3 75 mg/m2/day 1 130 mg/m2/day 1|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define the dose-limiting toxicity and maximum tolerated dose in phase I study To evaluate the overall response rate in phase II study |  | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) To evaluate the safety and tolerability of the treatment combination. 2) To estimate overall survival. 3) To estimate the time to progression and the duration of overall response. |  | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced gastric cancer with measurable disease, Docetaxel,Oxaliplatin, Phase I/II study, Advanced gastric cancer, First line treatment