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

NCT ID: NCT00876915

Last Updated: 2015-11-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 218 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Detailed 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.

Conditions

Venous Thromboembolism; Pulmonary Embolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

High Risk for VTE recieving dalteparin

Patients assigned at random to receive prophylactic dalteparin injections

Group Type: EXPERIMENTAL

dalteparin injection

Intervention Type: DRUG

Potency is described in international anti-Xa units (IU). One unit (anti-Xa) of dalteparin sodium, average molecular weight 5,000, corresponds to the activity of one unit of the 1st International Standard for Low Molecular Weight Heparin (LMWH)with respect to inhibition of coagulation Factor Xa in plasma utilizing the chromogenic peptide substrate S-2765 (N-alpha-Benzyloxycarbonyl-D-arginyl-glycyl-arginine-pNA.2HCl).

High Risk for VTE No therapy

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Low Risk for VTE

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

dalteparin injection

Potency is described in international anti-Xa units (IU). One unit (anti-Xa) of dalteparin sodium, average molecular weight 5,000, corresponds to the activity of one unit of the 1st International Standard for Low Molecular Weight Heparin (LMWH)with respect to inhibition of coagulation Factor Xa in plasma utilizing the chromogenic peptide substrate S-2765 (N-alpha-Benzyloxycarbonyl-D-arginyl-glycyl-arginine-pNA.2HCl).

Intervention Type: DRUG

Other Intervention Names

Fragmin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Charles Francis

Professor emeritus

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles W. Francis, MD

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Rochester Medical Center

Locations

University of California, Davis

Sacramento, California, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Rochester General Hospital

Rochester, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Duke University School of Medicine

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, Canada

Countries

United States; Canada

References

Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.

Reference Type: DERIVED

PMID: 33337539 (View on PubMed)

Khorana AA, Francis CW, Kuderer NM, Carrier M, Ortel TL, Wun T, Rubens D, Hobbs S, Iyer R, Peterson D, Baran A, Kaproth-Joslin K, Lyman GH. Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial. Thromb Res. 2017 Mar;151:89-95. doi: 10.1016/j.thromres.2017.01.009. Epub 2017 Jan 26.

Reference Type: DERIVED

PMID: 28139259 (View on PubMed)

Other Identifiers

1R01HL095109-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

25387

Identifier Type: -

Identifier Source: org_study_id