Randomized, Phase III-b, Multi-centre, Open-label, Parallel Study of Enoxaparin (Low Molecular Weight Heparin) Given Concomitantly With Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Gastric and Gastro-oesophageal Cancer
In the GASTRANOX study, patients will have inoperable (locally advanced) or metastatic newly
diagnosed gastric or gastro oesophageal cancer. These patients carry a definite thrombosis
risk. Patients will be scheduled to have at least 6 months of palliative chemotherapy.
During this period symptomatic thromboembolism will be common but currently no routine
prophylaxis is provided.
The dose of Enoxaparin to be evaluated in this study is 1mg/kg. This represents half of the
full treatment dose. For an average weight individual this will represent between 60 and 70
mg a day of Enoxaparin. The prophylactic dose for high-risk surgical patients in the United
States is 60mg total daily dosing of Enoxaparin per day. This high-risk dose has been shown
to be safe and effective in preventing thromboembolic disease in high-risk populations such
as those undergoing major elective orthopaedic surgery. An alternative for high-risk dose
is 40mg given once a day. This dose is also effective and safe. Thus the dose to be
provided in the GASTRANOX study is not markedly different from the high-risk doses already
in routine clinical practice either in North America (30mg twice a day - 60mg total daily
dosing) or 40mg once a day in Europe. It is also half of the full treatment dose which has
been shown to be effective and safe in the treatment of venous thromboembolism.
Since cancer patients are recognised to have bleeding risk it was felt inappropriate to
provide the full treatment dose of Enoxaparin. Thus half the full treatment doses provided.
On the other hand the biological effect of low molecular weight heparins in cancer suggests
that higher doses be given to enhance the potential survival benefit.
The study is intended to evaluate the safety and efficacy of the study drug compared to best
normal practice. The standard methodology for such a comparison is to conduct a randomized,
Multi-centre: It is anticipated that a single centre will be unable to recruit sufficient
subjects, in 1 year, to conduct the assessment and therefore multiple centres will be
recruited to conduct the study.
Open Label: All patients will receive standard care at their site. It would not be feasible
to expect placebo parenteral administration for six months. All VTE events will be
adjudicated. Mortality is an objective end-point.
Standard treatment control: subjects will be treated according to best practice with half
also receiving the study treatment.
Parallel-group: due to the nature of the condition this is the only practical design.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Event Free Survival (EFS) - Composite endpoint of overall survival plus free of symptomatic VTE .
up to 1 year from start of treatment
Ajay K Kakkar, PhD
Thrombosis Research Institute
India: Drugs Controller General of India