A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients (PHACS)

University of Rochester

Status and phase: Terminated; Phase 3

Conditions: Pulmonary Embolism; Venous Thromboembolism

Treatments: Drug: dalteparin injection

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00876915

1R01HL095109-01 (U.S. NIH Grant/Contract)

25387

Details and patient eligibility

About

Some cancer patients starting a new chemotherapy regimen are likely to develop blood clots, also known as venous thromboembolism (VTE). Blood clots can cause symptoms and can occasionally be life-threatening. The purpose of this study is to determine if a daily injection of a blood-thinner, dalteparin, for 12 weeks can safely and effectively reduce the frequency of blood clots. Dalteparin is currently approved for prevention of blood clots following surgery and in hospitalized patients but not specifically for cancer outpatients.

Full description

VTE is an increasingly frequent complication of cancer and anti-cancer therapies. It is associated with increased mortality and other significant adverse consequences. Risk factors for VTE in the cancer population have been identified, and multiple studies have also shown that VTE can be prevented in high-risk populations with the use of thromboprophylaxis. This study evaluated the safety and efficacy of prophylaxis in a high-risk subgroup of cancer patients identified by a validated risk model developed by us previously called the "Khorana Score." Correlative studies evaluated the value of tissue factor as a predictive biomarker of VTE. The purpose of this study was to conduct a prospective, randomized clinical trial comparing the safety and efficacy of prophylaxis with dalteparin to no treatment in reducing VTE in high-risk ambulatory cancer patients initiating chemotherapy and to establish the value of TF as a predictive marker for VTE in ambulatory cancer patients receiving chemotherapy.

PHACS was a randomized multi-center clinical trial. Eligible patients were enrolled and underwent baseline screening ultrasonography of the lower extremities to rule out pre-existing DVT and a chest CT scan to rule out PE. If negative, patients were then randomized to receive either dalteparin 5000 units subcutaneously daily or observation for a study period of 12 weeks. The first day of dalteparin prophylaxis coincided with the first day of initiation of a new systemic chemotherapy regimen. The patients were seen every 4 weeks (±1 week) at the time of regularly scheduled chemotherapy cycle visits for serial ultrasonography of lower extremities during study period (i.e. at 4, 8 and 12 weeks.) A chest CT scan was performed at 12 weeks. Compliance was measured by asking patients about missed doses at these 4-weekly visits as well as by asking patients to fill an injection diary.

Enrollment: 218 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• A histologic diagnosis of malignancy;
• At planned initiation of a new systemic chemotherapy regimen (including patients starting on first chemotherapy or patients previously treated but starting on a new regimen);
• A risk score for VTE ≥3 [assign score of 2 for very high risk sites of cancer (stomach, pancreas), score of 1 for high risk site (lung, lymphoma, gynecologic, bladder, testicular) and score of 0 for all other sites], hemoglobin <10 g/dL or planned use of erythropoiesis stimulating agents, platelet count ≥350,000/mm3, total leukocyte count > 11,000/mm3 or body mass index ≥ 35 kg/m2]. Any counts meeting criteria drawn within 2 weeks prior to enrollment are considered acceptable.
• Age 18 years or older
• Provide written, informed consent.

Exclusion criteria

• Active bleeding or at high risk of serious bleeding complication in the opinion of the investigator
• Diagnosis of primary brain tumor multiple myeloma, leukemia, or myelodysplastic syndrome
• Planned stem cell transplant
• Life expectancy < 6 months
• Known allergy to heparin or LMWH
• Patient or caregiver incapable of daily self-injection
• Acute or chronic renal insufficiency with creatinine clearance < 30 mL/min
• History of heparin-induced thrombocytopenia
• Allergy to contrast agents
• Pregnancy
• Need for anticoagulant therapy
• Platelet count < 75,000/mm3

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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218 participants in 3 patient groups

High Risk for VTE recieving dalteparin

Experimental group

Description:

Patients assigned at random to receive prophylactic dalteparin injections

Treatment:

Drug: dalteparin injection

High Risk for VTE No therapy

No Intervention group

Description:

No prophylactic therapy for VTE prevention given (Subjects receiving standard of care)

Low Risk for VTE

No Intervention group

Description:

Used as a control for the secondary outcome of evaluating tissue factor in collected blood samples