Trial record 1 of 1 for:    NCT00876915
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A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients (PHACS)

This study has been terminated.
(slow enrollment and lack of continuing funds)
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Eisai Inc.
Information provided by (Responsible Party):
Charles Francis, University of Rochester
ClinicalTrials.gov Identifier:
NCT00876915
First received: March 31, 2009
Last updated: October 28, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Venous Thromboembolism
Pulmonary Embolism
Drug: dalteparin injection
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Percentage of Patients With Venous Thromboembolisms [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    The percentage of patients who developed a Venous thromboembolism were recorded within 12 weeks following randomization including all adjudicated occurrences of symptomatic DVT, PE and upper extremity thrombus as well as all asymptomatic DVT and PE detected by lower extremity ultrasonography and chest CT.

  • Percentage of Patients Who Experienced Clinically Significant Bleeding Events. [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
    The percentage of patients who experienced a clinically significant bleeding event were recorded (including major and clinically significant non-major bleeding) over 13 weeks (12 weeks of study and an additional week of observation). Major bleeding was defined as being clinically overt and satisfying one of the following: decrease in hemoglobin of 2.0 g/dL, leading to transfusion of 2 or more units of blood or packed red cells, occurring in a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial) or leading to death. Clinically significant non-major bleeding was defined as clinically overt, not meeting criteria for major bleeding and with one of the following characteristics: multiple-source, spontaneous hematoma > 25 cm², epistaxis > 5 mins, macroscopic hematuria not related to instrumentation, spontaneous rectal bleeding, gingival bleeding > 5 mins, hemoptysis, hematemesis or prolonged bleeding (> 5 minutes) after venipuncture.


Secondary Outcome Measures:
  • The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of tissue factor ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of Tissue Factor at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients.

  • The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of D-Dimer ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of D-Dimer at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients

  • The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of Human F12 ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of Human F12 at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients

  • The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of TFPI ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of TFPI at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients

  • The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of FVIIa ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of FVIIa at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients

  • The Value of Thrombin Antithrombin (TAT) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients [ Time Frame: baseline value of TAT ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure the value of TAT at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients


Enrollment: 218
Study Start Date: July 2009
Study Completion Date: December 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Risk for VTE recieving dalteparin
Patients assigned at random to receive prophylactic dalteparin injections
Drug: 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).
Other Name: Fragmin
No Intervention: High Risk for VTE No therapy
No prophylactic therapy for VTE prevention given (Subjects receiving standard of care)
No Intervention: Low Risk for VTE
Used as a control for the secondary outcome of evaluating tissue factor in collected blood samples

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00876915

Locations
United States, California
University of California, Davis
Sacramento, California, United States, 95817
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Rochester General Hospital
Rochester, New York, United States, 14621
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University School of Medicine
Durham, North Carolina, United States, 27705
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Canada, Ontario
Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
University of Rochester
National Heart, Lung, and Blood Institute (NHLBI)
Eisai Inc.
Investigators
Principal Investigator: Charles W. Francis, MD Univeristy of Rochester Medical Center
  More Information

Responsible Party: Charles Francis, Professor emeritus, University of Rochester
ClinicalTrials.gov Identifier: NCT00876915     History of Changes
Other Study ID Numbers: 25387  1R01HL095109-01 
Study First Received: March 31, 2009
Results First Received: July 24, 2015
Last Updated: October 28, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
prevention of VTE and PE in high risk cancer patients

Additional relevant MeSH terms:
Pulmonary Embolism
Thromboembolism
Venous Thromboembolism
Cardiovascular Diseases
Embolism
Embolism and Thrombosis
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrin Modulating Agents
Fibrinolytic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 26, 2016