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

A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Fragmin (5,000 IU Subcutaneously) in Preventing Catheter-Related Complications When Given Daily to Cancer Patients With Central Venous Catheters

RATIONALE: The use of dalteparin may be able to prevent complications caused by the use of a catheter to supply chemotherapy to cancer patients. It is not yet known if dalteparin is effective in reducing these complications.

PURPOSE: Randomized phase III trial to determine the effectiveness of dalteparin in preventing catheter-related complications in cancer patients who are 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