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

March 31, 2009
October 28, 2015
July 2009
July 2014   (final data collection date for primary outcome measure)
  • 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.
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. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00876915 on ClinicalTrials.gov Archive Site
  • 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
To establish the value of tissue factor (TF) as a predictive marker for VTE in ambulatory cancer patients receiving chemotherapy. [ Time Frame: baseline evaluation of tissue factor and then monthly for 4 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Venous Thromboembolism
  • Pulmonary Embolism
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
  • Experimental: High Risk for VTE recieving dalteparin
    Patients assigned at random to receive prophylactic dalteparin injections
    Intervention: Drug: dalteparin injection
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
218
December 2014
July 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00876915
25387, 1R01HL095109-01
Yes
Not Provided
Not Provided
Charles Francis, University of Rochester
University of Rochester
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Eisai Inc.
Principal Investigator: Charles W. Francis, MD Univeristy of Rochester Medical Center
University of Rochester
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP