Chemotherapy for Patients With Cancer of the Stomach

Study Overview
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Brief Summary
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The purpose of this study is to determine maximal tolerable dose (MTD) of the combination of docetaxel, oxaliplatin and S1 (DOS) to patients with gastric cancer.

Detailed Description
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The primary aim of this dose-finding study is to determine the maximum tolerated doses of docetaxel, oxaliplatin and S1 given every second (DOS2w) or third (DOS3w) week as first-line treatment in patients with advanced gastro-esophageal cancer. Secondary end points are to evaluate toxicities according to NCI-CTCAE v. 4, response rate, progression-free survival and overall survival Primary Outcome Measure: To determine maximum tolerated dose (MTD) for the the combination regimes (DOS2w) and (DOS3w). The investigators have planned to examine 4 dose levels of (DOS2w) and 3 dose levels of (DOS3w). Methods: This dose-finding study is planned to include a total of 24 patients with advanced gastro-esophageal cancer, adenocarcinoma. 12 patients will be included in (DOS2w) at four at progressively higher dose levels. Chemotherapy will be repeated day 1 every second week to a maximum of nine courses. 12 patients will be included in (DOS3w) at three progressively higher dose levels. Chemotherapy will be repeated day 1 every third week to a maximum of six courses. In both (DOS2w) and (DOS3w) dose-limiting toxicity (DLT) will be evaluated after the first course. In case of DLT among one of the three patients during the first course of treatment additional three patients will be added at the respective dose level. Dose escalation is continues if 0/3 or 1/6 patients experience DLT. Patients will be evaluated with a ct-scan at baseline and after every three or four cycles to exclude progression and evaluate response. Response is assessed by the investigator according to RECIST version 1.1.

Official Title
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Phase I Trial With Docetaxel, Oxaliplatin and S1 as First-line Treatment for Patients With Non-resectable Adenocarcinoma of the Esophagus or Gastric

Conditions
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First-line Treatment for Patients With Non-resectable Gastric Cancer or Cancer of the Esophagus or

Intervention / Treatment
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* Drug: DOS2w Dose level 1A
* Drug: DOS2w Dose level 2A
* Drug: DOS2w Dose level 3A
* Drug: DOS2w Dose level 4A
* Drug: DOS3w Dose level 1B
* Drug: DOS3w Dose level 2B
* Drug: DOS3w Dose level 3B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven adenocarcinoma of the esophagus or the ventricle (ECV), and which cannot be treated curatively. Age ≥ 18 years. WHO performance status 0-1. Neutrophils ≥ 1,5 x 109/L and platelets ≥ 100 x 109/L. Bilirubin ≤ 1,5 x UNL (Upper Normal Limit) and ASAT and/or ALAT ≤ 3 x UNL. Creatinine-clearance ≥ 60 ml/min. Planned first day of treatment within 8 days after inclusion in the study. Signed consent form. Exclusion Criteria: No previous treatment with chemotherapy, except for (neo)-adjuvant chemotherapy for adenocarcinoma - treatment should have been completed at least 6 months before entrance in this study. No sensory neuropathy. No previously treatment with docetaxel, oxaliplatin or S1. No clinical suspicion of brain metastases. No cytotoxic treatment or other experimental treatment within 2 weeks of inclusion in the study. Other serious disease (i.e. heart disease, AMI within 1 year or ongoing infection). No pregnant women or women who are lactating. Patients who are not using contraception. No known DPD-deficiency or known allergy to taxanes or platinum. No signs of physical or mental illness that would prevent absorption of oral treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Sequential Assignment
Interventional Model Description: Two parallel phase 1/2a studies with 3+3 design with either DOS given every second week or every third week in Caucasian patients (Table 1). Patients were included into DOS2w and DOS3w in sequence. In the DOS2w group: Patients received escalating doses of Docetaxel (30-50 mg/m2 on Day 1), fixed doses of O (70 mg/ m2 on Day 1) and S-1 (30-35 mg/m2/day twice daily orally on Days 1-7) every two weeks. In the DOS3w group: Patients received escalating doses of docetaxel (40-60 mg/m2 on Day 1), fixed doses of O (100 mg/ m2 on Day 1) and S-1 (25 mg/m2/day twice daily orally on Days 1-14) every three weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DOS2W Dose level 1A<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks. | Drug: DOS2w Dose level 1A<br>* Docetaxel (30 mg/m2), Oxaliplatin (70 mg/m2) and S1 (60 mg/2) will be given every 2 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS2w 1A;|
| Experimental: DOS2W Dose level 2A<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks. | Drug: DOS2w Dose level 2A<br>* Docetaxel (30 mg/m2), Oxaliplatin (70 mg/m2) and S1 (70 mg/2) will be given every 2 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS2w 2A;|
| Experimental: DOS2W Dose level 3A<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks. | Drug: DOS2w Dose level 3A<br>* Docetaxel (40 mg/m2), Oxaliplatin (70 mg/m2) and S1 (70 mg/2) will be given every 2 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS2w 3A;|
| Experimental: DOS2W Dose level 4A<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 2 weeks. | Drug: DOS2w Dose level 4A<br>* Docetaxel (50 mg/m2), Oxaliplatin (70 mg/m2) and S1 (70 mg/2) will be given every 2 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS2w 4A;|
| Experimental: DOS3W Dose level 1B<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks. | Drug: DOS3w Dose level 1B<br>* Docetaxel (40 mg/m2), Oxaliplatin (100 mg/m2) and S1 (50 mg/2) will be given every 3 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS3w 1B;|
| Experimental: DOS3W Dose level 2B<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks. | Drug: DOS3w Dose level 2B<br>* Docetaxel (50 mg/m2), Oxaliplatin (100 mg/m2) and S1 (50 mg/2) will be given every 3 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS3w 2B;|
| Experimental: DOS3W Dose level 3B<br>Treatment with Docetaxel, Oxaliplatin and S1. Treatment is given every 3 weeks. | Drug: DOS3w Dose level 3B<br>* Docetaxel (60 mg/m2), Oxaliplatin (100 mg/m2) and S1 (50 mg/2) will be given every 3 weeks. In total there is 5 dose levels and if no patients experience DLT on a given level, next dose level will be administered.<br>* Other names: DOS3w 3B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival |  | Up to 2 years after first administration of DOS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Docetaxel, Gastric cancer, Cancer of the esophagus, Oxaliplatin, S1