FLOT vs. FLOT/Ramucirumab for Perioperative Therapy of Gastric or GEJ Cancer (RAMSES)
Condition: Stomach Cancer; Gastroesophageal Junction Cancer
MeSH terms: Stomach Neoplasms
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Previous studies provide a strong theoretical rationale for the conduct of a randomized study
      evaluating the efficacy and safety of ramucirumab in combination with FLOT in the
      perioperative treatment of resectable adenocarcinoma of the stomach or GEJ.
    

Detailed description: 
      This is a multicenter, randomized, controlled, open-label study including patients with
      locally advanced adenocarcinoma of the stomach and GEJ scheduled to receive perioperative
      chemotherapy.

      The scope of the phase II portion of the trial is to evaluate pathological response rates of
      either regimen assessed by a centralized pathology and evaluate safety and tolerability.

      Patients with locally advanced esophagogastric adenocarcinoma (i.e. cT2 any N or any T
      N-positive) with exclusion of distant metastases will be included in this trial.

      Patients will be centrally reviewed and then stratified by tumor site (GEJ vs. gastric),
      histological type (intestinal vs. diffuse/mixed or unknown) and clinical stage (T1/2 vs. T3/4
      and/or N+) and randomized 1:1 to receive either FLOT (Arm A) or FLOT/ramucirumab (Arm B).

      Arm A (FLOT) Patients randomized to Arm A will receive 4 pre-operative cycles (8 weeks) of
      biweekly FLOT (Docetaxel 50 mg/m² in 250 ml NaCl 0.9%, iv over 1 h; Oxaliplatin 85 mg/m² in
      500 ml G5%, iv over 2h; Leucovorin 200 mg/m² in 250 ml NaCl 0.9%, iv over 30 min; 5-FU 2600
      mg/m², iv over 24 h, q2wk) of the preoperative treatment phase. Surgery in Arm A is planned
      to occur 4 to 6 weeks after d1 of last FLOT. Patients will receive 4 additional
      post-operative cycles (8 weeks) of FLOT in the post-operative treatment phase. Post-operative
      treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.

      Arm B (FLOT/ramucirumab) Patients randomized to Arm B will receive ramucirumab 8mg/kg i.v.
      over 60 min in combination with the FLOT regimen, which is administered identical to Arm A as
      described above. Surgery in Arm B is planned to occur 4 to 6 weeks after d1 of last
      FLOT/ramucirumab dose (but never earlier than 4 weeks after d1 of last FLOT/ramucirumab
      dose). Patients will receive 4 additional post-operative cycles (8 weeks) of FLOT/ramucirumab
      in the post-operative treatment phase followed by a total of 16 cycles of ramucirumab as a
      monotherapy (q2wk), starting 2 weeks after d1 of the last cycle of FLOT/ramucirumab.

      In both of the arms, tumor assessments (CT or MRI) are performed before randomization and
      prior to surgery, and then every 3 months thereafter until progression/relapse, death or end
      of follow-up. A change from CT into MRI in the follow up period is possible at any time.

      During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to
      every treatment dose. Safety of FLOT/ramucirumab will be monitored continuously by careful
      monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
    

Intervention name(s): Docetaxel; Oxaliplatin; Calciumfolinat; 5-Fluorouracil; Ramucirumab
Intervention type(s): Drug; Drug; Drug; Drug; Biological
Intervention description(s): Docetaxel 50 mg/m², d1; Oxaliplatin 85 mg/m², d1; Leucovorin 200 mg/m², d1; 5-FU 2600 mg/m², d1; Ramucirumab 8mg/kg, d1
Other intervention name(s): TAXOTERE®; ELOXATIN®; Leucovorin; 5-FU
Intervention MeSH terms: Leucovorin; Docetaxel; Fluorouracil; Oxaliplatin; Ramucirumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment