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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

Phase 3
18 Years
75 Years
Open (Enrolling)
Gastric Cancer, Gastroesophageal Cancer

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Trial Information

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,
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.

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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

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

Outcome Time Frame:

up to 1 year from start of treatment

Safety Issue:


Principal Investigator

Ajay K Kakkar, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thrombosis Research Institute


India: Drugs Controller General of India

Study ID:




Start Date:

July 2008

Completion Date:

August 2010

Related Keywords:

  • Gastric Cancer
  • Gastroesophageal Cancer
  • Bleeding events
  • Stomach Neoplasms