Clinical trial NCT00876915: A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
Official title: A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Venous Thromboembolism
Pulmonary Embolism
Keywords: prevention of VTE and PE in high risk cancer patients
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eisai Inc.
First posted: 2009-04-07
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Percentage of Patients With Venous Thromboembolisms
timeFrame: 12 weeks
measure: Percentage of Patients Who Experienced Clinically Significant Bleeding Events.
timeFrame: 13 weeks
Secondary outcomes:
measure: The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of tissue factor
measure: The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of D-Dimer
measure: The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of Human F12
measure: The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of TFPI
measure: The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of FVIIa
measure: The Value of Thrombin Antithrombin (TAT) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
timeFrame: baseline value of TAT
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute (OHRI)
state: Ontario
Study officials:
affiliation: Univeristy of Rochester Medical Center
name: Charles W. Francis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.