FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of HER-2 Expressing Gastric or GEJ Cancer — PETRARCA  

Stomach Cancer Clinical Trial

Official title: FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of Adenocarcinoma of the Stomach and Gastroesophageal Junction Expressing HER-2. A Phase II/III Trial of the AIO.

Status Completed

Clinical Trial Summary

Previous studies provide a strong theoretical rationale for the conduct of a randomized study evaluating the efficacy and safety of Herceptin and pertuzumab in combination with FLOT in the perioperative treatment of resectable HER-2 positive adenocarcinoma of the stomach or GEJ.

Clinical Trial 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. According to centrally assessed HER-2 status: Patients with HER-2 positive tumors will receive FLOT +/- Herceptin / pertuzumab.

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 define 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 stratified by age (18-69 vs. ≥ 70), tumor site (GEJ vs. gastric) and clinical stage (T1/2 vs. 3/4 and N- vs. N+) and randomized 1:1 to receive either FLOT (Arm A) or FLOT/Herceptin/pertuzumab (Arm B).

Arm A (control group) Patients randomized to Arm A will receive 4 pre-operative treatments of FLOT (Docetaxel 50 mg/m², iv over 2 h; Oxaliplatin 85 mg/m² in 500 ml G5%, iv over 2h; Leucovorin 200 mg/m² in 250 ml NaCl 0.9 %, iv over 1 h; 5-FU 2600 mg/m², iv over 24 h) on d1, d15, d29, d43 of the preoperative treatment phase. Surgery is recommended to occur 4 weeks after last FLOT (4 weeks after d43 = day 71). Patients will receive 4 additional post-operative treatments of FLOT on d1, d15, d29, and d43 of the post-operative treatment phase. Post-operative treatment should start 6 to 8 weeks, but at maximum 12 weeks after surgery.

Arm B (Herceptin/pertuzumab group) Patients randomized to Arm B will receive the FLOT regimen identical to Arm A as described above in conjunction with three-weekly Herceptin at 8mg/kg initial dose (Day 1, loading dose) followed by subsequent doses of Herceptin at 6mg/kg on d22 and d43 and pertuzumab at 840mg on d1, d22, and d43. Surgery is recommended to occur 4 weeks after last FLOT/Herceptin/pertuzumab dose (4 weeks after d43 = day 71). Patients will receive 3 additional doses of Herceptin and pertuzumab on d1, d22, and d43 of the post-operative treatment phase, together with the postoperative chemotherapy. Moreover, patients will receive 11 additional doses of Herceptin and pertuzumab after the end of post-operative FLOT.

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.

During treatment, clinical visits (blood cell counts, detection of toxicity) occur prior to every treatment dose. Safety of FLOT/Herceptin/pertuzumab will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported. ;

Related Conditions & MeSH terms

• Gastroesophageal Junction Cancer
• Stomach Cancer
• Stomach Neoplasms

• NCT number: NCT02581462
• Study type: Interventional
• Source: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2016
• Completion date: July 17, 2020