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)

January 2, 2020 updated by: Sook Ryun Park, Asan Medical Center

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

176

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Xarelto
Drug: apixaban
10 mg q12 hours for 7days followed by 5mg q12 hours for 21 weeks
Other Names:
  • eliquis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months
Rate of total event of bleeding
Time Frame: 6 months
6 months
Time to major bleeding event
Time Frame: 6 months
6 months
Time to clinical relevant bleeding event
Time Frame: 6 months
6 months
Time to total event of bleeding
Time Frame: 6 months
6 months
Rate of recurrent or aggravated venous thromboembolism
Time Frame: 6 months
6 months
Time to recurrent or aggravated venous thromboembolism
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2017

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

September 30, 2021

Study Registration Dates

First Submitted

May 2, 2017

First Submitted That Met QC Criteria

May 2, 2017

First Posted (Actual)

May 4, 2017

Study Record Updates

Last Update Posted (Actual)

January 6, 2020

Last Update Submitted That Met QC Criteria

January 2, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S2017-0327

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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