NCT02661971

FLOT vs. FLOT/Ramucirumab for Perioperative Therapy of Gastric or GEJ Cancer (RAMSES)

Perioperative RAMucirumab in Combination With FLOT Versus FLOT Alone for reSEctable eSophagogastric Adenocarcinoma - RAMSES - a Phase II/III Trial of the AIO

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 180 (actual)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Stomach Cancer
• Gastroesophageal Junction Cancer

Interventions

Type	Name	Description
DRUG	Docetaxel	Docetaxel 50 mg/m², d1
DRUG	Oxaliplatin	Oxaliplatin 85 mg/m², d1
DRUG	Calciumfolinat	Leucovorin 200 mg/m², d1
DRUG	5-Fluorouracil	5-FU 2600 mg/m², d1
BIOLOGICAL	Ramucirumab	Ramucirumab 8mg/kg, d1

Timeline

• Start date: 2016-06-01
• Primary completion: 2021-12-01
• Completion: 2022-06-20
• First posted: 2016-01-25
• Last updated: 2022-07-11

Locations

2 sites across 2 countries: Germany, Italy