TOPGEAR

Protocol Title

TOP GEAR: Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma

A randomised II/III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer.

Publication Reference

Leong T, Smithers BM, Haustermans K, Michael M, Gebski V, Miller D, Zalcberg J, Boussioutas A, Findlay M, O’Connell RL, Verghis J, Willis D, Kron T, Crain M, Murray WK, Lordick F, Swallow C, Darling G, Simes J, Wong R. TOPGEAR: a randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Annals of Surgical Oncology. Published online 25 Mar 2017.

Leong T, Smithers BM, Michael M, Gebski V, Boussoutias A, Miller D, Simes J, Zalcberg J, Hausterman K, Lordick F, Schuhmacher C, Swallow C, Darling G, Wong R. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG). BMC Cancer 2015; 15: 532.

Conference Presentation Reference

Goldstein D, Fawcett J, Bridgewater JA, Choti M, Wilson K, Gebski V, Aiken C, Eminton Z, Falk S, Stanton L, Primrose JN. Feasibility of trials to assess safety and toxicity of peri-operative and post-operative adjuvant therapy for hepatic metastases from colorectal cancer. European Cancer Congress 2015; 25-29  Sep 2015; Vienna

Verghis J, Miller D, Smithers BM, Murray WK, Crain M, Leong T. Conducting quality assurance processes in a multimodality treatment study involving chemoradiotherapy and surgery—measuring data integrity in the TOPGEAR trial. ACTA 2015 International Clinical Trials Symposium; 7–10 Oct 2015; Sydney.

Leong T, Smithers M, Michael M, Gebski V, Boussioutas A, Miller D, Zalcberg J, Wong R, Haustermans K. TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG). American Society of Clinical Oncology Annual Meeting; 1–5 Jun 2012; Chicago.

Aim

The purpose 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 (pCR) rates in the first instance, and subsequently overall survival, in patients undergoing adequate surgery (D1+ dissection) for resectable gastric cancer.

Background

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 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%.

An important question that needs to be addressed is whether chemoradiotherapy is superior to chemotherapy alone in the neoadjuvant treatment of resectable gastric cancer.

The interventional arm of 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 outcome of the trial may contribute to the improvement of survival rates of patients who undergo gastric surgery.

Clinical Trial Design

TOP GEAR is a multicentre, prospective, randomised, stratified, phase II/III clinical trial.

Eligible patients, with resectable adenocarcinoma of the stomach or gastroesophageal junction, will be randomly allocated to one of two treatment groups to receive:

(1) Perioperative chemotherapy alone (control arm). This may comprise 3 pre-operative and 3 post-operative cycles of ECF, ECX or EOX; or 4 pre-operative and 4 post-operative cycles of FLOT. ; or

(2) Perioperative chemotherapy plus preoperative chemoradiation (experimental arm).

In the experimental chemoradiation arm, patients will undergo the following treatment schedule. Patients will receive one of 4 different standard chemotherapy regimens (ECF, ECX, EOX or FLOT) at the discretion of their treating clinician. Patients may receive 2 cycles of ECF, ECX or EOX at three weekly intervals before their operation. Alternatively, they may receive 3 cycles of FLOT at two weekly intervals before their operation. They will have a 2–4 week break between the last chemotherapy treatment and starting chemoradiotherapy. Following chemoradiotherapy, patients should have up to six weeks break between chemoradiotherapy and surgery.Patients will then commence 3 post-operative cycles of ECF, ECX or EOX, or 4 post-operative cycles of FLOT, between 4-10 weeks after surgery.

The acceptable types of resection surgery are a total gastrectomy, subtotal gastrectomy and an oesophago-gastrectomy. There will be three years of follow up.

Patients Recruited

Click here to access the table and view recruitment data on all AGITG open trials:

Open Trial Recruitment Table

Contact Email

Principal Investigator

Professor Trevor Leong (Peter MacCallum Cancer Centre, Melbourne VIC)

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

Cancer Australia through The Priority-driven Collaborative Cancer Research Scheme.
Cancer Council Australia.
National Health and Medical Research Council.