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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
574
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)
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.
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.
Calvary Mater Newcastle
Newcastle, New South Wales, Australia
Chris O Brien Lifehouse
Sydney, New South Wales, Australia
Liverpool Hospital
Sydney, New South Wales, Australia
Nepean Hospital
Sydney, New South Wales, Australia
Prince of Wales Hospital
Sydney, New South Wales, Australia
Royal North Shore Hospital
Overall survival
The interval from the date of randomisation to the date of death from any cause, or the date last known alive.
Time frame: Up to 5 years
Disease free survival
The time from the date of randomisation to the first observation of disease progression or death due to any cause.
Time frame: Up to 5 years
Pathological response rate
The extent of reduction in tumour size following pre-operative treatment, as determined by macroscopic and microscopic assessment of the tumour.
Time frame: At time of surgery
Proportion of participants with given grades of toxicities
The proportion of participants starting at least one cycle of treatment and the grades of the toxicities reported.
Time frame: Up to 5 years
Surgical complete resection rate (R0)
The complete macroscopic resection of gross tumour with negative surgical margins.
Time frame: At the time of surgery
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Sydney, New South Wales, Australia
St George Hospital
Sydney, New South Wales, Australia
Westmead Hospital
Sydney, New South Wales, Australia
The Tweed Hospital
Tweed Heads, New South Wales, Australia
Wollongong Hospital
Wollongong, New South Wales, Australia
...and 49 more locations