Overall Survival of Inoperable Gastric/GastroOesophageal Cancer Subjects on Treating With LMWH + Chemotherapy(CT) vs Standard CT (GASTRANOX)
Due to evidence available both in terms of efficacy and safety of low molecular weight heparin, its use for the prevention of thromboembolic disease in cancer patients undergoing surgical intervention, and its extended use in higher doses for the prevention of recurrent thromboembolism in cancer patients with established thrombosis, with a view that the potential benefits for survival in cancer patients from low molecular weight heparin therapy comes because of a biological activity, the dose of 1mg/Kg (50% of the full treatment dose) for a period of 6 months coincident with 6 cycles of chemotherapy, has been chosen for this study.
Drug: Standard Chemotherapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||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|
- Event Free Survival (EFS) - Composite endpoint of overall survival plus free of symptomatic VTE . [ Time Frame: up to 1 year from start of treatment ] [ Designated as safety issue: No ]
- Incidence of SVTE Overall survival Major and minor haemorrhages during chemotherapy and / or up to 30 days after last dose is provided. Serious adverse events, All reported adverse events HIT [ Time Frame: upto 1 year from the start of treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2008|
|Study Completion Date:||August 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Active Comparator: B
Standard Chemotherapy (upto 6 cycles)
Drug: Standard Chemotherapy
Enoxaparin: 1 mg/kg once daily in addition to standard chemotherapy up to 6 months
Once daily dose of 1mg/Kg of body weight for 6 months
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, comparative study.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00718354
|Mahatma Gandhi Cancer Hospital & Research Institute ,1/7 M.V.P. Colony, - ,, .|
|Vishakhapattanam, Andhra Pradesh, India, 530017|
|Mahavir Cancer Sansthan,Phulwari Sharif|
|Patna, Bihar, India, 801505|
|Gujarat Cancer Research Institute, Civil Hospital Campus,Asarwa, ,|
|Ahmedabad, Gujarat,, India, 380016|
|Department Of Radiotherapy,S.S.G. Hospital, -|
|Baroda,Vadodara, Gujarat,, India, 390 001|
|Gokula Curie Cancer Centre,M.S.Ramaiah Memorial Hospital,MSR Nagar, MSRIT Post|
|Bangalore, Karnataka, India, 560054|
|Trivandrum, Kerala,, India, 695011|
|MGM Medical College & MY Hospital,|
|Indore, M.P, India, 452005|
|Curie Manavta Cancer Centre, Opp.Hotel Sandeep Naka,Nashik|
|Mumbai, Maharashtra,, India, 425004|
|Ruby Hall Clinic,Cancer Building,40 sassoon Road, , ,|
|Pune, Maharashtra, India, 411001|
|Cancer Hospital & Research Institute, Cancer Hill|
|Gwalior, MP, India, 474009|
|Acharya Tulsi Regional Cancer Treatment & Research Institute|
|Bikaner, UP, India|
|B.P.Poddar Hospital & Medical Research Ltd,71/1, Humayun Kabir Sarani,, Block-G, New Alipore|
|Kolkata, west Bangol, India, 700053|
|Calcutta, West Bengal, India|
|Chittaranjan National Cancer Institute,37, S.P.Mukhurjee Road|
|Kolkata, West Bengal, India, 700026|
|Dr. BRA IRCH,all India Institute of Medical Sciences,Ansari Nagar,|
|New Delhi, India, 110029.|
|Principal Investigator:||Ajay K Kakkar, PhD||Thrombosis Research Institute|