Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma
Conditions
Gastric Cancer
Conditions: official terms
Stomach Neoplasms
Conditions: Keywords
Gastric cancer, Stomach cancer, Chemoradiotherapy, Surgery, Chemotherapy, Neoadjuvant
Study Type
Interventional
Study Phase
Phase 2/Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Epirubicin + cisplatin + 5-fluorouracil Type: Drug
Name: Preoperative chemoradiotherapy Type: Radiation
Name: Gastric resection Type: Procedure
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) that is:

1. Stage IB (T1N1 only, T2N0 not eligible) - IIIC, i.e. T3 - T4 and/or node positive, according to American Joint Committee on Cancer (AJCC) 7th edition.

2. Considered operable following initial staging investigations (surgeon believes that an R0 resection can be achieved) (GEJ tumours are defined as tumours that arise in the cardia or at the GEJ that do not involve more than 2cm of the lower esophagus, i.e. Siewert Type II and Siewert Type III)

- Age >=18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Adequate organ function defined as follows:

1. Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 10⁹ /L, White blood cell count >=3 x 10⁹ /L, Platelet count >=100 x 10⁹ /L

2. Hepatic: Serum bilirubin <=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine transaminase (ALT) <=3.0 x ULN

3. Renal: Serum creatinine <=0.150 mmol/L, Calculated creatinine clearance >=50 mL/min

- Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation

- Any patient with a history of ischaemic heart disease and abnormal ECG, or who is over 60 years of age should have a pre-treatment evaluation of cardiac function with a multigated acquisition (MUGA) scan or echocardiogram. Patients will only be included if the left ventricular ejection fraction is >=50%.

- Written informed consent obtained before randomization

- Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice adequate contraceptive measures.

Exclusion Criteria:

- Evidence of metastatic disease

- Prior chemotherapy or radiotherapy

- Patients with a past history of cancer in the 5 years before randomization except for the following. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, and patients with carcinoma in situ of the cervix that has been treated by operation only are eligible, even if they were diagnosed and treated within the 5 years before randomization.

- Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled

- Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures

- Cardiac failure and other contraindications to epirubicin

- Patients with impaired gastrointestinal absorption for whatever reason

- Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons:

1. Clinically significant sensorineural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin)

2. Severe tinnitus

3. Renal impairment (GFR <=50ml/min)

4. Peripheral neuropathy >=grade 2

5. Inability to tolerate intravenous hydration e.g due to cardiac disease

6. Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin.
Locations
Calvary Mater Newcastle
Newcastle, New South Wales, Australia
Status: Recruiting
Liverpool Hospital
Sydney, New South Wales, Australia
Status: Recruiting
Nepean Hospital
Sydney, New South Wales, Australia
Status: Recruiting
Prince of Wales Hospital
Sydney, New South Wales, Australia
Status: Recruiting
Royal North Shore Hospital
Sydney, New South Wales, Australia
Status: Recruiting
Royal Prince Alfred Hospital
Sydney, New South Wales, Australia
Status: Recruiting
St George Hospital
Sydney, New South Wales, Australia
Status: Recruiting
Westmead Hospital
Sydney, New South Wales, Australia
Status: Recruiting
The Tweed Hospital
Tweed Heads, New South Wales, Australia
Status: Recruiting
Wollongong Hospital
Wollongong, New South Wales, Australia
Status: Recruiting
Princess Alexandra Hospital
Brisbane, Queensland, Australia
Status: Recruiting
Flinders Medical Centre
Adelaide, South Australia, Australia
Status: Recruiting
Royal Hobart Hospital
Hobart, Tasmania, Australia
Status: Recruiting
Launceston General Hospital
Launceston, Tasmania, Australia
Status: Recruiting
Geelong Hospital
Geelong, Victoria, Australia
Status: Recruiting
Austin Hospital
Melbourne, Victoria, Australia
Status: Recruiting
Monash Medical Centre
Melbourne, Victoria, Australia
Status: Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Status: Recruiting
St Vincent's Hospital
Melbourne, Victoria, Australia
Status: Recruiting
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Status: Recruiting
Royal Perth Hospital
Perth, Western Australia, Australia
Status: Recruiting
Auckland Hospital
Auckland, New Zealand
Status: Recruiting
Christchurch Hospital
Christchurch, New Zealand
Status: Recruiting
Dunedin Hospital
Dunedin, New Zealand
Status: Recruiting
Waikato Hospital
Waikato, New Zealand
Status: Recruiting
Start Date
September 2009
Completion Date
December 2020
Sponsors
Australasian Gastro-Intestinal Trials Group
Source
Australasian Gastro-Intestinal Trials Group
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page