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
Intervention: 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 description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Gastric cancer; Cancer of the esophagus; Oxaliplatin; Docetaxel; S1

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.
    

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