S1201: Combination Chemo for Patients W/Advanced or Metastatic Esophageal, Gastric, or Gastroesophageal Junction Cancer
Condition: Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer; Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil,
      irinotecan hydrochloride, and docetaxel, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Combining more than one
      drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy
      is more effective in treating tumor cells.

      PURPOSE: This randomized phase II trial studies how well oxaliplatin, leucovorin calcium, and
      fluorouracil work compared to irinotecan hydrochloride and docetaxel in treating patients
      with esophageal cancer, gastric cancer, or gastroesophageal junction cancer.
    

Detailed description: 
      OBJECTIVES:

        -  To assess progression-free survival of high-excision repair cross-complementing 1(ERCC1)
           patients with advanced or metastatic cancer of the esophagus, stomach, or
           gastroesophageal junction (GEJ) treated with FOLFOX comprising oxaliplatin, leucovorin
           calcium, and fluorouracil compared to those treated with irinotecan hydrochloride plus
           docetaxel.

        -  To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
           cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to those treated
           with irinotecan hydrochloride plus docetaxel.

        -  To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
           cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to high-ERCC1
           patients treated with FOLFOX.

        -  To assess overall survival of and toxicities in each of the two treatment arms in this
           group of patients.

        -  To assess the response probability (confirmed and unconfirmed, complete and partial
           responses) in the subset of patients with measurable disease in each of the two
           treatment arms.

        -  To explore whether there is evidence of interaction between treatment arm and ERCC1
           expression in this group of patients. (Exploratory)

        -  To bank tissue and blood for future translational medicine studies; a) To explore the
           relationship of ERCC-1 and ERCC-2 single nucleotide polymorphism (SNP) genotypes with
           clinical outcome in these patients; and b) To explore the association between germline
           variations in these SNPs and ERCC-1 mRNA expression in these patients. (Exploratory)

      OUTLINE: This is a multicenter study. Patients are stratified according to ERCC1 expression
      (high [≥ 1.7] vs low [< 1.7]), and disease site (esophageal vs gastric/gastroesophageal
      junction). Patients are randomized to 1 of 2 treatment arms.

        -  Arm I (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV
           over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Courses repeat
           every 14 days in the absence of disease progression or unacceptable toxicity.

        -  Arm II: Patients receive irinotecan hydrochloride IV over 90 minutes and docetaxel IV
           over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of
           disease progression or unacceptable toxicity.

      Blood and tumor tissue samples may be collected for ERCC1 expression analysis and future
      research studies.

      After completion of study treatment, patients are followed up every 3 months for up to 3
      years.
    

Intervention name(s): FOLFOX regimen; docetaxel; fluorouracil; irinotecan hydrochloride; leucovorin calcium; oxaliplatin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Given IV. Fluorouracil, oxaliplatin, & leucovorin calcium.; 30 mg/m^2, IV over 30 minutes on Day 1,8 of each 21 day cycle.; 400 mg/m^2, IV bolus on Day 1 of each 14 day cycle; 2400 mg/m^2 IV over 46-48 hours on Days 1-2 of each 14 day cycle.; 65 mg/m^2, IV over 90 minutes on Days 1 & 8 of every 21 day cycle.; 400 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.; 85 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.
Other intervention name(s): Taxotere; RP56976; NSC-628503; 5-fluorouracil; 5-FU; NSC-19893; CPT-11; NSC-616348; NSC-3590; Eloxatin; NSC-266046
Intervention MeSH terms: Leucovorin; Docetaxel; Fluorouracil; Oxaliplatin; Irinotecan; Calcium; Levoleucovorin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent esophageal cancer; stage IV esophageal cancer; recurrent gastric cancer; stage IV gastric cancer; adenocarcinoma of the gastroesophageal junction; stage IIIB gastric cancer; stage IIIC gastric cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer; adenocarcinoma of the esophagus; adenocarcinoma of the stomach