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Evaluation of Dalteparin for Long-term (One Year) Treatment of Blood Clots in Subjects With Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00942968
First Posted: July 21, 2009
Last Update Posted: February 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  Purpose
The purpose of this study is to determine the long term tolerability and safety of dalteparin in subjects with cancer.

Condition Intervention Phase
Cancer Drug: dalteparin Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: FRAG-A001-401: Dalteparin Sodium Injection (Fragmin), Multicenter, Open-Label, Single-arm, Long Term (52 Weeks) Study for Understanding the Safety and Efficacy in Subjects With Malignancies and Symptomatic Venous Thromboembolism

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee [ Time Frame: Month 2 up to Month 6 ]
    A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.

  • Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee [ Time Frame: Month 7 up to Month 12 ]
    A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.

  • Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee [ Time Frame: Month 7 up to Month 12 ]
    VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported.


Secondary Outcome Measures:
  • Number of Participants With Investigator Identified Major Bleeding Events [ Time Frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 ]
    A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported.

  • Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12 ]
    A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported.

  • Number of Participants With Fatal Bleeding Events [ Time Frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 ]
    Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported.

  • Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 12 ]
    Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death.

  • Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 12 ]
    Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding.

  • Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) [ Time Frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 ]
    VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported.

  • Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 ]
    VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported.

  • Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) [ Time Frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 ]
    VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported.

  • Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 12 ]
    Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram.

  • Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee [ Time Frame: Month 1 up to Month 12 ]
    Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography.


Other Outcome Measures:
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline (Day 1) up to Week 52 ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

  • Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Baseline (Day 1) up to Week 52 ]
    Criteria for abnormality: Hemoglobin greater than or equal to(>=)130*lower limit of normal(LLN); less than or equal to(<=)170*upper limit of normal(ULN), hematocrit >=0.39*LLN;<=0.51*ULN, red blood cell >=4.5*LLN;<=5.9*ULN, platelet>=150*LLN;<= 450*ULN, white blood cells >=4*LLN;<=11*ULN; lymphocytes>=0.09;<=0.44, neutrophils=>0.16*LLN;<=0.7*ULN, eosinophils<=0.04*ULN, basophils<=0.02*ULN, monocytes>0.08*ULN; bilirubin >=5.1*LLN;<=22.2*ULN, aspartate aminotransferase >=13*LLN;<=36*ULN, alanine aminotransferase>=11*LLN;<=54*ULN, alkaline phosphatase>=31*LLN ;<=104 *ULN, total protein>=60*LLN; <=76*ULN, albumin=>35*LLN;<=50*ULN, glucose>=3.77 ;<=6.05;blood urea nitrogen>=1.785*LLN;<=7.5*ULN, creatinine>=70.7*LLN;<=114.9*ULN, creatinine kinase>=30*LLN ;<=280*ULN, lactate dehydrogenase>=85*LLN;<=180*ULN, sodium>=137*LLN ;<=144*ULN, potassium >=3.5*LLN;<=5*ULN, chloride>=102*LLN;<=111*ULN, calcium>=2.22*LLN ;<=2.57*ULN, phosphorus=>0.81 ;<=1.45); nitrogen cholesterol>=1.78*LLN ;<=7.49*ULN.

  • Number of Participants With Abnormal Physical Examinations Findings [ Time Frame: Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52 ]
    Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status [used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead]). Abnormality in physical examinations was based on investigator's discretion.

  • Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings [ Time Frame: Baseline up to Week 52 ]
    Clinically significant ECG findings included: corrected QT (QTc) > 450 ms, QTc >500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.

  • Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants [ Time Frame: Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]
    Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age.


Enrollment: 338
Study Start Date: June 2009
Study Completion Date: June 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: dalteparin
Daily subcutaneous injection 200IU/kg dalteparin

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects, age greater than or equal to 18 years of age.
  2. Females should be either of non-childbearing potential as a result of surgery, radiation therapy, menopause (one year post onset), or of childbearing potential and willing to adhere to an acceptable method of pregnancy prevention.
  3. Subjects must be newly diagnosed, symptomatic proximal deep-vein thrombosis of the lower extremity, pulmonary embolism, or both.
  4. Subjects must have active malignancy defined as a diagnosis of cancer (excluding basal cell or squamous cell carcinoma of the skin) within six months before enrollment, having received any treatment for cancer within the previous six months, or having documented recurrent or metastatic cancer.
  5. Prior to enrollment, subjects must not have received therapeutic doses of anticoagulant therapy (including low molecular weight heparin [LMWH]) for >48 hours (or >4 doses within 48 hours).
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  7. Subjects must have a life expectancy of >6 months.
  8. Subjects must have a platelet count of >75,000 mm^3.
  9. The subject must not be on any oral anticoagulant therapy for concomitant diseases.
  10. Subjects must have no active or serious bleeding episodes within two weeks prior to study entry.
  11. Subjects must be able to comply with scheduled follow-ups.

Exclusion Criteria:

  1. Subjects who have a high risk of serious bleeding (e.g., recent neurosurgery within 30 days, history of intracranial hemorrhage, acute gastroduodenal ulcer, etc.).
  2. Subjects who are on hemodialysis.
  3. Subjects who have a prior placement of a Greenfield filter or other device to prevent embolization of deep vein thromboses.
  4. Subjects with a known contraindication to the use of heparin (e.g., heparin-induced thrombocytopenia).
  5. Subjects with a known hypersensitivity to heparin, dalteparin sodium, other LMWHs or pork products.
  6. Subjects who are currently participating in another clinical trial involving anticoagulation therapy (with the exception of acetylsalicylic acid (ASA) in the 30 days prior to study entry, or who are actively using any investigational drugs/treatments 30 days prior to study entry involving anticoagulation therapy (with the exception of ASA , t.i.d).
  7. Subject is pregnant or breast feeding.
  8. Subjects with uncontrolled hypertension characterized by a sustained systolic pressure >170 mmHg and/or diastolic pressure >100 mmHg.
  9. Subjects with a serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject's ability to complete the study.
  10. Any condition that makes the subject unsuitable in the opinion of the investigator.
  11. Subjects with leukemia or myeloproliferative syndrome.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00942968


  Hide Study Locations
Locations
United States, Arizona
Arizona Cancer Center
Tuscon, Arizona, United States, 85719
United States, California
Bay Area Cancer Research Group
Pleasant Hill, California, United States, 94523
Harbor-UCLA Medical Center
Torrance, California, United States, 90509
United States, Connecticut
University of CT Health Center
Farmington, Connecticut, United States, 6030
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, United States, 6360
United States, District of Columbia
Georgetown University Hospital-Lombardi Cancer Ctr
Washington, District of Columbia, United States, 20007
United States, Florida
Halifax Health
Daytona Beach, Florida, United States, 32114
United States, Georgia
Atlanta Institute for Medical Research
Decatur, Georgia, United States, 30030
United States, Illinois
Orchard Healthcare Research Inc.
Skokie, Illinois, United States, 60076
United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Bringham and Women's Hospital
Boston, Massachusetts, United States, 2115
United States, Michigan
Henry Ford Hospital K-15
Detroit, Michigan, United States, 48202
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Stony Brook University, Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, North Dakota
MidDakota Clinic
Bismarck, North Dakota, United States, 58501
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Vermont
Vermont Cancer Center at Fletcher Allen Health Care
Burlington, Vermont, United States, 5401
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Austria
LKH Graz Univrsitatstklinik fur Innere Medizin
Graz, Austria
Medizinische Universitat Innsbruck Studienambulanz Hamatologie
Innsbruck, Austria
KH d. Elizabethinen Linz GmbH Servicestelle fur klin. Studien und Universitare Angelegenheiten
Linz, Austria
KH der Barmherzigen Schwestern
Linz, Austria
Dialysestation Landesklinkum St.Poelten
St. Poelten, Austria
Medizinische Universitat Wien
Vienna, Austria
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada
Ottawa Health Research Institute
Ottawa, Ontario, Canada
University Health Network-Toronto General Hospital
Toronto, Ontario, Canada
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada
Sir Mortimer B. Davis Jewish General Hospital
Montreal, Quebec, Canada
Netherlands
Gelre Ziekenhuizen-Locatie Apeldoorn
Apeldoorn, Netherlands
Orbis Medisch Centrum, Sittard-Geleen
Sittard-Geleen, Netherlands
Spain
Hospital clinic i Provincial de Agencia de Ensayos Clinicos
Barcelona, Spain
Hospital General Santa Maria del Rosell
Caragena (Murcia), Spain
Hospital Virgen de la Arrixaca
El Palmar (Murcia), Spain
Hospital Universitari Dr Josep Trueta
Girona, Spain
Clinica Universitaria de Navarra
Pamplona, Spain
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
Study Director: Gary Palmer, MD Medical Affairs, Eisai, Inc
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00942968     History of Changes
Other Study ID Numbers: FRAG-A001-401
A6301095 ( Other Identifier: Alias Study Number )
First Submitted: July 16, 2009
First Posted: July 21, 2009
Results First Submitted: January 4, 2017
Results First Posted: February 24, 2017
Last Update Posted: February 24, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action