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

NCT00718354 | Completed Phase 3 DMC

• 1 other identifier: TRI0702
• Study Type: interventional
• Target: 740
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Gastric Cancer; Gastroesophageal Cancer

Keywords

Bleeding events

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS) - Composite endpoint of overall survival plus free of symptomatic VTE .

  up to 1 year from start of treatment

Secondary Outcomes (1)

• 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

  upto 1 year from the start of treatment

Study Arms (2)

B

ACTIVE COMPARATOR

Standard Chemotherapy (upto 6 cycles)

Drug: Standard Chemotherapy

A

EXPERIMENTAL

Enoxaparin: 1 mg/kg once daily in addition to standard chemotherapy up to 6 months

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

Once daily dose of 1mg/Kg of body weight for 6 months

A

Standard Chemotherapy DRUG

Investigator's discretion

Also known as: 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

B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thrombosis Research Institute: lead

Study Sites (15)

Mahatma Gandhi Cancer Hospital & Research Institute ,1/7 M.V.P. Colony, - ,, .

Vishakhapattanam, Andhra Pradesh, 530017, India

Location

Mahavir Cancer Sansthan,Phulwari Sharif

Patna, Bihar, 801505, India

Location

Gujarat Cancer Research Institute, Civil Hospital Campus,Asarwa, ,

Ahmedabad, Gujarat, 380016, India

Location

Department Of Radiotherapy,S.S.G. Hospital, -

Baroda,Vadodara, Gujarat, 390 001, India

Location

Gokula Curie Cancer Centre,M.S.Ramaiah Memorial Hospital,MSR Nagar, MSRIT Post

Bangalore, Karnataka, 560054, India

Location

Madhavan J.P.

Trivandrum, Kerala, 695011, India

Location

MGM Medical College & MY Hospital,

Indore, M.P, 452005, India

Location

Cancer Hospital & Research Institute, Cancer Hill

Gwalior, Madhya Pradesh, 474009, India

Location

Curie Manavta Cancer Centre, Opp.Hotel Sandeep Naka,Nashik

Mumbai, Maharashtra, 425004, India

Location

Ruby Hall Clinic,Cancer Building,40 sassoon Road, , ,

Pune, Maharashtra, 411001, India

Location

Acharya Tulsi Regional Cancer Treatment & Research Institute

Bikaner, Uttar Pradesh, India

Location

B.P.Poddar Hospital & Medical Research Ltd,71/1, Humayun Kabir Sarani,, Block-G, New Alipore

Kolkata, West Bangol, 700053, India

Location

Chittaranjan National Cancer Institute,37, S.P.Mukhurjee Road

Kolkata, West Bengal, 700026, India

Location

Biswajit Sanyal

Kolkata, West Bengal, India

Location

Dr. BRA IRCH,all India Institute of Medical Sciences,Ansari Nagar,

New Delhi, 110029., India

Location

Related Publications (18)

• Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66. doi: 10.1016/s0959-8049(01)00267-2. No abstract available.

  PMID: 11602373 BACKGROUND

• Lee YJ, Jy W, Horstman LL, Janania J, Reyes Y, Kelley RE, Ahn YS. Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias. Thromb Res. 1993 Nov 15;72(4):295-304. doi: 10.1016/0049-3848(93)90138-e.

  PMID: 8303669 BACKGROUND

• Powell J, McConkey CC. The rising trend in oesophageal adenocarcinoma and gastric cardia. Eur J Cancer Prev. 1992 Apr;1(3):265-9. doi: 10.1097/00008469-199204000-00008.

  PMID: 1467772 BACKGROUND

• Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. doi: 10.3322/canjclin.50.1.7.

  PMID: 10735013 BACKGROUND

• Cohen AT, Wagner MB, Mohamed MS. Risk factors for bleeding in major abdominal surgery using heparin thromboprophylaxis. Am J Surg. 1997 Jul;174(1):1-5. doi: 10.1016/S0002-9610(97)00050-0.

  PMID: 9240942 BACKGROUND

• Ajani JA. Chemotherapy for gastric carcinoma: new and old options. Oncology (Williston Park). 1998 Oct;12(10 Suppl 7):44-7.

  PMID: 9830625 BACKGROUND

• Panzini I, Gianni L, Fattori PP, Tassinari D, Imola M, Fabbri P, Arcangeli V, Drudi G, Canuti D, Fochessati F, Ravaioli A. Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses. Tumori. 2002 Jan-Feb;88(1):21-7.

  PMID: 12004845 BACKGROUND

• Petralia GA, Lemoine NR, Kakkar AK. Mechanisms of disease: the impact of antithrombotic therapy in cancer patients. Nat Clin Pract Oncol. 2005 Jul;2(7):356-63. doi: 10.1038/ncponc0225.

  PMID: 16075795 BACKGROUND

• Thodiyil PA, Kakkar AK. Variation in relative risk of venous thromboembolism in different cancers. Thromb Haemost. 2002 Jun;87(6):1076-7. No abstract available.

  PMID: 12083490 BACKGROUND

• Mismetti P, Laporte S, Darmon JY, Buchmuller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001 Jul;88(7):913-30. doi: 10.1046/j.0007-1323.2001.01800.x.

  PMID: 11442521 BACKGROUND

• Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A, Dietrich-Neto F; ENOXACAN II Investigators. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002 Mar 28;346(13):975-80. doi: 10.1056/NEJMoa012385.

  PMID: 11919306 BACKGROUND

• Rasmussen MS. Does prolonged thromboprophylaxis improve outcome in patients undergoing surgery? Cancer Treat Rev. 2003 Jun;29 Suppl 2:15-7. doi: 10.1016/s0305-7372(03)80004-x.

  PMID: 12887945 BACKGROUND

• Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, Rustin G, Thomas M, Quigley M, Williamson RC. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol. 2004 May 15;22(10):1944-8. doi: 10.1200/JCO.2004.10.002.

  PMID: 15143088 BACKGROUND

• Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, Cetin M, Soyuer S. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost. 2004 Aug;2(8):1266-71. doi: 10.1111/j.1538-7836.2004.00871.x.

  PMID: 15304029 BACKGROUND

• Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. doi: 10.1056/NEJMoa025313.

  PMID: 12853587 BACKGROUND

• 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.

  BACKGROUND

• von Tempelhoff GF, Harenberg J, Niemann F, Hommel G, Kirkpatrick CJ, Heilmann L. Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial. Int J Oncol. 2000 Apr;16(4):815-24. doi: 10.3892/ijo.16.4.815.

  PMID: 10717252 BACKGROUND

• Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. doi: 10.1200/JCO.2005.03.133. Epub 2005 Feb 7.

  PMID: 15699480 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Enoxaparin; Epirubicin; Cisplatin; Capecitabine; XELOX; Carboplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes

Study Officials

• Ajay K Kakkar, PhD

  Thrombosis Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 18, 2008
• Study Start: July 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 13, 2015

Record last verified: 2015-05

Locations

IN (15)