Protocol title: 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.
Study Chair: A/Professor Trevor Leong (Peter MacCallum Cancer Centre, Melbourne VIC)
Associate Oncology Program Manager: Danielle Miller
Trial Coordinator: Sarah York
Detailed information available on the Australian and New Zealand Clinical Trials Registry — TOP GEAR
Cancer Australia: $541,183 (2009) $756,137 (2014)
Cancer Council: $18,480 (2009), $18,480 (2010), $17,557 (2011), $924.67 (2012)
The primary objective is to investigate whether the addition of chemoradiotherapy is superior to chemotherapy alone in the neoadjuvant setting by improving pathological complete response (pCR) rates in the first instance, and subsequently overall survival, in patients undergoing adequate surgery (D1+ dissection) for resectable gastric cancer.
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%, a figure that has improved little over the past 30 years. Despite this rather grim outlook, there have been several important recent advances utilising chemotherapy and radiotherapy in the adjuvant setting that have generated renewed interest and debate in the treatment of resectable gastric cancer.
Since the publication of the INT0116 and MAGIC studies, clinicians have been faced with the dilemma of which adjuvant strategy to employ. Opinions remain divided regarding the relative efficacy of chemoradiation vs chemotherapy and clinical practice varies amongst different institutions. The important question that needs to be addressed is whether chemoradiotherapy is superior to chemotherapy alone in the neoadjuvant treatment of resectable gastric cancer.
This is an international, intergroup trial led by investigators from the AGITG and the NHMRC Clinical Trials Centre, in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), the European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group (NCIC CTG) in Canada.
TOP GEAR is a multicentre, prospective, randomised, stratified, phase II/III clinical trial. The trial will be conducted in two parts. Part 1 is the phase II component of the trial that will recruit 120 patients, while Part II is the phase III component that will recruit a further 632 patients to provide a total sample size of 752 patients.
Eligible patients will be randomly allocated to one of 2 treatment groups, that is, preoperative chemotherapy or preoperative chemoradiation.
ECF : Epirubicin 50mg/m2 IV day 1, Cisplatin 60mg/m2 IV day 1, 5-Fluorouracil 200mg/m2/d IV 21 day continuous infusion. OR
ECX : Epirubicin 50mg/m2 IV day 1, Cisplatin 60mg/m2 IV day 1, Capecitbine (Xeloda) 625mg/m2 bid days 1-21
PR-EOP CRT: Continuous infusional 5-FU — 200mg/m2/day, 7 days per week throughout the entire period of radiotherapy via CADD pump through PICC line,
OR Capecitabine 825mg/m2, bid, days 1 to 5 of radiotherapy
Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.
The acceptable resections are a total gastrectomy, a subtotal gastrectomy, and an esophago-gastrectomy (Ivor-Lewis esophago-gastrectomy for gastroesophageal junction [GEJ] cancers [Siewert Type II and Siewert Type III] invading up to but no more than 2cm of the lower esophagus). It is considered that 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 GEJ cancers requiring an esophago-gastrectomy.
The total number of patients expected to be recruited are 752 over 5 years with 3 years of follow-up.
To view the Study Schema click here.