Dalteparin to Prevent Complications in Cancer Patients Receiving Chemotherapy Through a Catheter

OBJECTIVES: I. Determine if dalteparin will reduce the incidence of clinically significant
catheter related complications (i.e., asymptomatic catheter related thrombosis) in cancer
patients receiving chemotherapy through a central venous catheter.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to treatment center and catheter placement (proximal to axilla vs
distal to axilla). Patients are randomized to one of two treatment arms. Arm I: Patients
receive dalteparin subcutaneously (SC) daily. Arm II: Patients receive placebo SC daily.
Treatment continues for 16 weeks or until catheter removal in the absence of unacceptable
toxicity. Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 345 patients (230 in arm I and 115 in arm II) will be accrued
for this study over 6 months.

Inclusion Criteria:

- Histologically confirmed malignancy

- No more than 5 days since placement of central venous catheter for administration of
chemotherapy

- Expected length of catheter use at least 16 weeks

- 18 and over

- Performance status: ECOG 0-2

- Life expectancy: At least 16 weeks

- Hematopoietic:

- Platelet count at least 100,000/mm3

- Absolute neutrophil count at least 1,500/mm3

- No known coagulopathy

- Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) except in case
of Gilbert's syndrome

- AST no greater than 3 times ULN (no greater than 5 times ULN in case of liver
metastases)

- PT/PTT no greater than 1.5 times ULN Renal:

- Creatinine no greater than 2 times ULN Cardiovascular:

- HIV negative

- Must weigh at least 90 pounds

- At least 3 months since prior eye, ear, or CNS surgery Other:

- At least 30 days since prior aspirin, dipyridamole, unfractionated heparin, other low
molecular weight heparins, or other anticoagulation therapy (except heparin flushing)

Exclusion Criteria:

- uncontrolled hypertension, unstable angina, or symptomatic congestive heart failure

- myocardial infarction in past 6 months

- uncontrolled cardiac arrhythmia Other:

- known hypersensitivity (including heparin induced thrombocytopenia) to dalteparin,
heparin, or other low molecular weight heparins

- active uncontrolled infection, including existing catheter related infection

- CNS trauma in past 3 months

- retinal detachment in past 6 months

- mental incapacitation or psychiatric illness that would preclude study compliance

- other serious concurrent disease that would preclude study participation

- active gastrointestinal or genitourinary tract bleeding

- intracranial or intraocular hemorrhage in past year

- concurrent high dose chemotherapy with stem cell transplantation

- concurrent induction/consolidation chemotherapy for leukemia

- concurrent high dose chemotherapy with stem cell transplantation