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A Randomized Phase II Open Label Study to Compare the Safety and Efficacy of Subcutaneous Dalteparin Versus Direct Oral Anticoagulants for Cancer-associated Venous Thromboembolism (PRIORITY)

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ClinicalTrials.gov Identifier: NCT03139487
Recruitment Status : Recruiting
First Posted : May 4, 2017
Last Update Posted : January 6, 2020
Sponsor:
Information provided by (Responsible Party):
Sook Ryun Park, Asan Medical Center

Brief Summary:
This is an open label, multi-center, and randomized phase II trial designed to compare the safety and efficacy of direct oral anticoagulants and subcutaneous dalteparin in patients with acute venous thromboembolism and upper gastrointestinal, hepatobiliary, or pancreatic cancer, based on a group sequential design. Enrolled patients will be randomized in a 1:1 ratio. Patients will be stratified by performance status, type of cancer, chemotherapy and medical centers.

Condition or disease Intervention/treatment Phase
Cancer-associated Thrombosis Esophageal Cancer Stomach Cancer Hepatocellular Carcinoma Pancreatic Cancer Duodenal Cancer Esophagogastric Junction Cancer Malignant Gastrointestinal Stromal Tumor Ampulla of Vater Cancer Biliary Cancer (Cholangiocarcinoma, Gall Bladder Cancer) Drug: Rivaroxaban Drug: Dalteparin Drug: apixaban Phase 2

Detailed Description:

This randomized II clinical trial will enrol patients with advanced upper gastrointestinal, hepatobiliary and pancreatic cancer who have venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis. Patients will be randomized in a 1:1 ratio and stratified by performance status, type of cancer and medical centers. The enrolled patients will receive either subcutaneous dalteparin or DOAC(rivaroxaban, apixavan) according to randomization until the end of planned treatment schedules (six months), recurrence of VTE, clinical relevant bleeding, major bleeding, death or discontinuation of study treatment for any other reason (e.g. withdrawal of consent or discretion of the investigator). The primary end-point is the rate of clinical relevant bleeding event as defined as overt bleeding which was associated with medical intervention. In addition to time to clinical relevant bleeding event, time to event of major bleeding, total bleeding including minor event, time to recurrent VTE, overall bleeding rate and overall VTE recurrent rate will be analyzed to compare safety and efficacy of both anticoagulants. The final analysis will be conducted when the last enrolled patient has an event or has completed as least six months follow up in the study. Patients without bleeding and recurrent VTE events at data cut-off are censored at the last date the patient is known to be free of events.

Planned interim analysis will be conducted in the intentions to treatment analysis set. The interim analysis for the randomized portion of the study will be performed when at least 40% of estimated bleeding events have been observed. The purpose of interim analysis is for early stopping of the study for safety. This study will use a Data Monitoring Committee.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Open Label Study to Compare the Safety and Efficacy of Subcutaneous Dalteparin Versus Direct Oral Anticoagulants for Cancer-associated Venous Thromboembolism in Patients With Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY
Actual Study Start Date : August 7, 2017
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021


Arm Intervention/treatment
Active Comparator: Low molecular weight heparin
Dalteparin, 200 IU/kg subcutaneously once daily for 4 weeks followed by 150 IU/kg once daily for 20 weeks
Drug: Dalteparin
200 IU/kg q24 hours for 4 weeks followed by 150 IU/kg q24 hours for 20 weeks
Other Name: Fragmin

Experimental: Direct oral anticoagulant

Rivaroxaban, 15 mg orally twice daily for 3 weeks followed by 20mg once daily for 21 weeks

Apixaban, 10 mg orally twice daily for 7days followed by 5mg twice daily for 21 weeks

Drug: Rivaroxaban
15 mg q12 hours for 3 weeks followed by 20mg q24 hours for 21 weeks
Other Name: Xarelto

Drug: apixaban
10 mg q12 hours for 7days followed by 5mg q12 hours for 21 weeks
Other Name: eliquis




Primary Outcome Measures :
  1. Rate of clinical relevant bleeding [ Time Frame: 6 months ]
    Clinically relevant bleeding: overt bleeding which was associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of anticoagulation, or associated with any other discomfort such as pain or impairment of activities of daily life, including major bleeding


Secondary Outcome Measures :
  1. Rate of major bleeding [ Time Frame: 6 months ]
    Major bleeding: Contributing to death, associated with a fall in hemoglobin ≧ 2 g/dL, or leading to transfusion of ≧ 2 units of red cells or if bleeding is intracranial, retroperitoneal, or another critical site.

  2. Rate of total event of bleeding [ Time Frame: 6 months ]
  3. Time to major bleeding event [ Time Frame: 6 months ]
  4. Time to clinical relevant bleeding event [ Time Frame: 6 months ]
  5. Time to total event of bleeding [ Time Frame: 6 months ]
  6. Rate of recurrent or aggravated venous thromboembolism [ Time Frame: 6 months ]
  7. Time to recurrent or aggravated venous thromboembolism [ Time Frame: 6 months ]


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.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed locally advanced or metastatic active cancer including Esophageal cancer, Esophagogastric junction cancer, Stomach cancer, Gastrointestinal stromal disease, Ampulla of Vater cancer, Duodenal cancer, Hepatocelluar carcinoma, Biliary cancer (cholangiocarcinoma, gall bladder cancer), Pancreatic cancer
  • Newly diagnosed deep vein thrombosis in any site and/or pulmonary thromboembolism on the basis of CT or doppler ultrasound image with or without symptoms
  • Male or female ≥ 18 years, < 80 years old age
  • Adequate major organ function including the following: Hematopoietic function: Platelet ≥ 75,000/mm3, Hepatic function: alanine aminotransferase levels 3 x upper limit of normal (if, with liver metastasis, alanine aminotransferase levels 5 x upper limit of normal), Aspartate Transaminase levels 3 x upper limit of normal (if, with liver metastasis, Aspartate Transaminase levels 5 x upper limit of normal), Renal function: estimated glomerular filtration rate ≥ 30 ml/min, Adequate coagulation time: prothrombin time ≤ 2 international normalized ratio, activated partial thromboplastin time 1.5 x upper limit of normal
  • Able to understand and comply with the requirement of the study and to provide written informed consent

Exclusion Criteria:

Patients will be excluded from the study for any of the following reasons:

  • Hemodynamically unstable pulmonary thromboembolism
  • Use with P-gp and strong CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) or inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort)
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g. patients with partial or total gastrectomy can enter the study, but not those with a jejunostomy probe), or inability to take oral medication
  • Patients with current bleeding
  • Recent history of major or uncontrolled bleeding within the previous 4 weeks
  • Severe malnutrition, BMI < 16
  • Patients who are receiving a therapeutic dose of rivaroxaban, low molecular weight heparin, fondaparinux, or unfractionated heparin for more than 72 hours before enrollment
  • Administration of a fibrinolytic agent for treatment of the current episode
  • Uncontrolled systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg
  • Patients who have to keep concurrent antiplatelet agent (e.g. aspirin, clopidogrel)
  • Patients who have clinical significant liver cirrhosis (Child Pugh score ≥ 7)
  • Inadequate cardiovascular function: New York Heart Association class III or IV heart disease, Unstable angina or myocardial infarction within the past 6 months, History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality
  • Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy, including infective endocarditis
  • History of or current brain metastases
  • Life expectancy less than 3 months

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): NCT03139487


Contacts
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Contact: Sook Ryun Park, M.D., Ph.D. +82-2-3010-3210 srpark@amc.seoul.kr
Contact: Seyoung Seo, M.D. syseo@amc.seoul.kr

Locations
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Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Sook Ryun Park       srpark@amc.seoul.kr   
Sponsors and Collaborators
Asan Medical Center
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Responsible Party: Sook Ryun Park, Associated professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT03139487    
Other Study ID Numbers: S2017-0327
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: January 6, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Sook Ryun Park, Asan Medical Center:
Anticoagulant Adverse Reaction
Cancer-associated Thrombosis
Low molecular weight heparin
Direct oral anticoagulant
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Gastrointestinal Stromal Tumors
Stomach Neoplasms
Gallbladder Neoplasms
Duodenal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Biliary Tract Neoplasms
Intestinal Neoplasms
Cholangiocarcinoma
Thrombosis
Thromboembolism
Venous Thromboembolism
Digestive System Diseases
Endocrine System Diseases
Adenocarcinoma
Carcinoma
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Gastrointestinal Diseases
Stomach Diseases