NCT01924819

Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma

A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 574 (actual)
• Sponsor: Australasian Gastro-Intestinal Trials Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Gastric cancer remains a significant global public health problem. Although in developed countries its incidence has dramatically decreased, on a worldwide scale it is still a leading cause of cancer-related deaths. Surgery is the only potentially curative treatment for gastric cancer. Although the survival rates for patients with early stage disease (stage 1A and 1B) are good, this subgroup of patients constitutes only 20% of those undergoing resection. The majority of patients will have locally advanced or metastatic disease at presentation, which has an extremely poor prognosis. The current five-year survival rate for gastric cancer in Western countries is approximately 20-30%, a figure that has improved little over the past 30 years. The intervention arm in TOPGEAR consists of pre-operative chemotherapy, pre-operative chemoradiotherapy, surgery and post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery and post-operative chemotherapy. The primary objective of TOPGEAR is to investigate whether the addition of chemoradiotherapy to chemotherapy is superior to chemotherapy alone in the neoadjuvant setting by improving pathological complete response rates in the first instance, and subsequently overall survival, in patients undergoing adequate surgery (D1+ dissection) for resectable gastric cancer.

Detailed description

Purpose: The purpose of this phase II/III clinical trial is to determine if pre-operative chemoradiotherapy improves overall survival in participants with resectable gastric cancer. Trial details: Participants will be randomised to receive either pre-operative chemotherapy or pre-operative chemoradiotherapy. The will undergo surgery and then receive further post-operative chemotherapy. Participants will be followed up for 5 years after treatment.

Conditions

• Gastric Cancer

Interventions

Type	Name	Description
DRUG	Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel	Epirubicin 50 mg/m2 IV day 1, cisplatin 60 mg/m2 IV day 1, 5-fluorouracil 200 mg/m2/d IV 21 day continuous infusion (ECF chemotherapy). Epirubicin 50 mg/m2 IV day 1, Cisplatin 60 mg/m2 IV day 1, Capecitabine (X = Xeloda) 625mg/m2, bid days 1-21 (ECX chemotherapy) Epirubicin 50mg/m2 IV day 1, Oxaliplatin (O) 130mg/m2 IV day 1, Capecitabine 625mg/m2, bid days 1-21 (EOX chemotherapy) 5-Fluorouracil 2600 mg/m² IV 24 h infusion day 1, Leucovorin (L) 200 mg/m² IV day 1, Oxaliplatin 85 mg/m² IV day 1, Docetaxel (T) 50 mg/m² IV day 1 (FLOT chemotherapy)
RADIATION	Preoperative chemoradiotherapy	Chemotherapy: Continuous infusional 5-fluorouracil 200mg/m2/day, 7 days per week, throughout the entire period of radiotherapy or capecitabine 825 mg/m2, oral tablet twice daily, days 1-5 of each week of radiotherapy (without weekends). Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.
PROCEDURE	Gastric resection	The acceptable resections are a total gastrectomy, a subtotal gastrectomy, and an esophagogastrectomy (Ivor-Lewis esophagogastrectomy for gastroesophageal junction cancers \[Siewert Type II and Siewert Type III\] invading up to but no more than 2cm of the lower esophagus). The minimum extent of the operation should be a D1+ lymph node dissection but it is recommended that a D2 dissection be performed or a D1+ for gastroesophageal junction cancers requiring an esophagogastrectomy.

Timeline

• Start date: 2009-09-01
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2013-08-19
• Last updated: 2025-03-04

Locations

59 sites across 10 countries: Australia, Belgium, Canada, Czechia, France, Germany, Israel, New Zealand, Slovenia, Spain