Chemotherapy for Patients With Cancer of the Stomach
Condition: First-line Treatment for Patients With Non-resectable Gastric Cancer or Cancer of the Esophagus or
MeSH terms: Stomach Neoplasms; Esophageal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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: 
      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.
    

Intervention name(s): DOS2w Dose level 1A; DOS2w Dose level 2A; DOS2w Dose level 3A; DOS2w Dose level 4A; DOS3w Dose level 1B; DOS3w Dose level 2B; DOS3w Dose level 3B
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.; 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.; 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.; 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.; 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.
Other intervention name(s): DOS2w 1A; DOS2w 2A; DOS2w 3A; DOS2w 4A; DOS3w 1B; DOS3w 2B; DOS3w 3B
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention 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)
Primary purpose: Treatment
Keywords: Gastric cancer; Cancer of the esophagus; Oxaliplatin; Docetaxel; S1