Overall Survival of Inoperable Gastric/GastroOesophageal Cancer Subjects on Treating With LMWH + Chemotherapy(CT) vs Standard CT (GASTRANOX)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Thrombosis Research Institute.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Thrombosis Research Institute
ClinicalTrials.gov Identifier:
NCT00718354
First received: July 16, 2008
Last updated: January 5, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Gastroesophageal Cancer
Drug: Enoxaparin
Drug: Standard Chemotherapy
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Thrombosis Research Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 740
Study Start Date: July 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
Standard Chemotherapy (upto 6 cycles)
Drug: Standard Chemotherapy
Investigator's discretion
Other Names:
  • Some commonly prescribed Chemotherapy regimens in India are:
  • - Epirubicin + Cisplatin + Capecitabine
  • - Capecitabine + Oxaliplatin
  • - Docetaxil + Carboplatin
  • - Epirubicin + Cisplatin + Fluorouracil
  • - Docetaxil + Cisplatin with G/C/S/F support
  • - Epirubicin + Cisplatin + Flourouracil
  • - Docetaxil + Cisplatin + Flourouracil
Experimental: A
Enoxaparin: 1 mg/kg once daily in addition to standard chemotherapy up to 6 months
Drug: Enoxaparin
Once daily dose of 1mg/Kg of body weight for 6 months

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent
  • Male or Female of age 18-75 years
  • Histologically confirmed gastric or gastro-oesophageal carcinoma.
  • Adenocarcinoma of the stomach stage III or IV considered inoperable at presentation.
  • ECOG performance status ≤ 1
  • Criteria for chemotherapy fulfilled (haematological, hepatic, renal).
  • Ability to receive daily injection (self-injection or by patient relative).
  • Urine-Pregnancy test negative.
  • Consent to the use of Contraceptive for women of child bearing age group

Exclusion Criteria:

  • History of previous malignancy within the previous 5 years (except curatively treated carcinoma in situ of the uterine cervix, or basal cell carcinoma of the skin), or concomitant malignancy.
  • Prior treatment with chemotherapy or radiotherapy if relapse less than 6 months
  • Non-epithelial gastric tumours, borderline tumours.
  • Medically unstable patients, including but not limited to those with active infection, acute hepatitis, gastrointestinal bleeding, uncontrolled cardiac arrhythmias, interstitial lung disease, inflammatory bowel disease, uncontrolled angina, uncontrolled hypercalcaemia, uncompensated congestive heart failure, uncontrolled diabetes, persistent renal failure, dementia, seizures, superior vena cava syndrome.
  • Persistent renal failure (persistent value of the calculated creatinine clearance < 30 mL/min defined as a documented value < 30 mL/min on at least 2 occasions ≥ 3 days prior entry into the study).
  • Prosthetic heart valves.
  • Any evidence of active bleeding disorder or risk of bleeding identified on fibroscopy done as a routine investigation before the consent for the trial. Fibroscopy is not mandatory to be done for the trial
  • Current, objectively-verified DVT, PE or other clinically significant thrombosis.
  • Documented previous episode of heparin-induced thrombocytopenia and/or thrombosis (HIT, HAT, or HITTS).
  • Contraindications to anticoagulation
  • Coagulopathies (acquired or inherited)
  • Prior history of cerebral hemorrhage or neurosurgery within the previous month
  • Bacterial endocarditis
  • Uncontrolled arterial hypertension (systolic BP:200 mmHg or diastolic BP:110 mmHg) at 2 successive readings
  • Haemostatic abnormalities: circulating anticoagulant, baseline platelet count <50 000/mm3, activated partial thromboplastin time (aPTT) value 1.5 x the upper limit of normal, or International Normalized Ratio (INR) >1.5. The laboratory test valid would be no earlier than 14 days for this criterion.
  • Indication for thrombolytic therapy
  • Any long-term anticoagulant therapy for medical condition.
  • Immunocompromised subjects, such as subjects with known HIV and those who have either had an AIDS-defining condition (e.g. Kaposi's sarcoma, Pneumocystitis carinii pneumonia) or have CD4 + T-lymphocyte count < 200 /mm3.
  • Known hypersensitivity to heparin, or LMWH, or pork derived products.
  • Body weight >100 kg.
  • Pregnant or lactating women.
  • Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling to be tested for pregnancy (pregnancy status should be checked by serum or urine pregnancy testing prior to exposure to the investigational product
  • Participation in another clinical trial (study medications / study devices) within the previous 30 days. (Surgical trials are allowed).
  • Psychiatric disorders of altered mentation that would preclude understanding of the informed consent process.
  • Psychological, familial, sociological, or geographical conditions, which do not permit treatment and/or medical follow-up required to comply with the study protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00718354

Contacts
Contact: Janice M Maganji, MBBS 00447824836535 mmaganji@tri-london.ac.uk

Locations
India
Mahatma Gandhi Cancer Hospital & Research Institute ,1/7 M.V.P. Colony, - ,, . Recruiting
Vishakhapattanam, Andhra Pradesh, India, 530017
Contact: Voonna Murlikrishna, MD    0091 9848191287    m_voonna@yahoo.com   
Principal Investigator: Murlikrishna Voonna, MD         
Mahavir Cancer Sansthan,Phulwari Sharif Recruiting
Patna, Bihar, India, 801505
Contact: J K Singh J.K., MD    0091 9431021001    drjksingh147@hotmail.com   
Principal Investigator: J K Singh, MD         
Gujarat Cancer Research Institute, Civil Hospital Campus,Asarwa, , Recruiting
Ahmedabad, Gujarat,, India, 380016
Contact: Kirti Patel, MD    0091 9825386037    drkirtimpatel@yahoo.co.in   
Principal Investigator: Kirti Patel, MD         
Department Of Radiotherapy,S.S.G. Hospital, - Recruiting
Baroda,Vadodara, Gujarat,, India, 390 001
Contact: Batra Vimal, MD    0091 9825350509    vimalbatra@rediffmail.com   
Principal Investigator: Vimal Batra, MD         
Gokula Curie Cancer Centre,M.S.Ramaiah Memorial Hospital,MSR Nagar, MSRIT Post Recruiting
Bangalore, Karnataka, India, 560054
Contact: Kilara Nalini, MD    0091 8023609999    nalini_kilara@yahoo.com   
Principal Investigator: Nalini Kilara, MD         
Madhavan J.P. Recruiting
Trivandrum, Kerala,, India, 695011
Contact: J.P Madhavan    0091 9447217437    jpmadhavan@hotmail.com   
Principal Investigator: J P Madhavan, MD         
MGM Medical College & MY Hospital, Recruiting
Indore, M.P, India, 452005
Contact: D.K Jain    0091 9425056828    alkadevendra@gmail.com   
Principal Investigator: D K Jain, MD         
Curie Manavta Cancer Centre, Opp.Hotel Sandeep Naka,Nashik Recruiting
Mumbai, Maharashtra,, India, 425004
Contact: Nagarakar Raj, MD    0091 9823061929    drrajnagarkar@yahoo.co.in   
Principal Investigator: Raj Nagarakar, MD         
Ruby Hall Clinic,Cancer Building,40 sassoon Road, , , Recruiting
Pune, Maharashtra, India, 411001
Contact: Hegde Sujai, MD    0091 9890107621    sujai_hegde@hotmail.com   
Principal Investigator: Sujai Hedge, MD         
Cancer Hospital & Research Institute, Cancer Hill Recruiting
Gwalior, MP, India, 474009
Contact: B R Shrivastav, MD    0091 9425109172    br_shrivastav08@yahoo.com   
Principal Investigator: B R Shrivastav, MD         
Acharya Tulsi Regional Cancer Treatment & Research Institute Recruiting
Bikaner, UP, India
Contact: R K Chaudhary, MD    0091 9414314294    drrkchaudhary@rediffmail.com   
Principal Investigator: R K Chaudhary, MD         
B.P.Poddar Hospital & Medical Research Ltd,71/1, Humayun Kabir Sarani,, Block-G, New Alipore Recruiting
Kolkata, west Bangol, India, 700053
Contact: Goswami Chanchal, MD    0091 9830055035    chanchalg@sify.com   
Principal Investigator: Chanchal Goswami, MD         
Biswajit Sanyal Recruiting
Calcutta, West Bengal, India
Contact: Biswajit Sanyal, MD         
Principal Investigator: Biswajit Sanyal, MD         
Chittaranjan National Cancer Institute,37, S.P.Mukhurjee Road Recruiting
Kolkata, West Bengal, India, 700026
Contact: Majumdar Jahar, MD    0091 9830028571    madhuchandakar@yahoo.com   
Principal Investigator: Jahar Majumdar, MD         
Dr. BRA IRCH,all India Institute of Medical Sciences,Ansari Nagar, Recruiting
New Delhi, India, 110029.
Contact: Atul Sharma, MD    0091 9868398328    atul1@hotmail.com   
Principal Investigator: Atul Sharma, MD         
Sponsors and Collaborators
Thrombosis Research Institute
Investigators
Principal Investigator: Ajay K Kakkar, PhD Thrombosis Research Institute
  More Information

Publications:
Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000; 50(1):7-33
Klerk CPW SS, Otten JMM, Buller HR, on behalf of the MALT Stusy Group. Malignancy and low molwcular weight heparin therapy: the MALT trial. Phathophysiology of Haemostasis and Thrombosis 2003; 33(Suppl 1):75.
Lee AYY RF, Julian JA, Gent M, Baker RI, Bowden C, et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of outsubjects with cancer and venous thromboembolism. Journal of Clinical Oncology 2005; 23(10):1-7.

Responsible Party: Prof A K Kakkar, Thrombosis Research Institute
ClinicalTrials.gov Identifier: NCT00718354     History of Changes
Other Study ID Numbers: TRI0702
Study First Received: July 16, 2008
Last Updated: January 5, 2010
Health Authority: India: Drugs Controller General of India

Keywords provided by Thrombosis Research Institute:
Bleeding events

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Capecitabine
Cisplatin
Epirubicin
Heparin, Low-Molecular-Weight
Dalteparin
Enoxaparin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Hematologic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 01, 2014