A Randomized Phase II Study to Compare the Safety and Efficacy of Dalt

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A Randomized Phase II Study to Compare the Safety and Efficacy of Dalteparin vs. Rivaroxaban for Cancer-associated Venous Thromboembolism (PRIORITY)

https://clinicaltrials.gov/ct2/show/NCT03139487

Purpose
This is an open label, multi-center, and randomized phase II trial designed to compare the safety and efficacy of oral rivaroxaban 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 (ECOG performance status 0-1 versus ≥2) and type of cancer.

Condition Intervention Phase
Cancer-associated Thrombosis
Esophageal Cancer
Gastric Cancer
Hepatobiliary Cancer
Pancreatic Cancer
Duodenal Cancer
Drug: Rivaroxaban
Drug: Dalteparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Phase II Open Label Study to Compare the Safety and Efficacy of Subcutaneous Dalteparin Versus Oral Rivaroxaban for Cancer-associated Venous Thromboembolism in Patients With Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer (PRIORITY)

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners
Drug Information available for: Rivaroxaban
Genetic and Rare Diseases Information Center resources: Esophageal Cancer Stomach Cancer
U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
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:
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.

Rate of total event of bleeding [ Time Frame: 6 months ]
Time to major bleeding event [ Time Frame: 6 months ]
Time to clinical relevant bleeding event [ Time Frame: 6 months ]
Time to total event of bleeding [ Time Frame: 6 months ]
Rate of recurrent or aggravated venous thromboembolism [ Time Frame: 6 months ]
Time to recurrent or aggravated venous thromboembolism [ Time Frame: 6 months ]

Estimated Enrollment: 176
Anticipated Study Start Date: May 2017
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Rivaroxaban
15 mg q12 hours for 3 weeks followed by 20mg q24 hours for 21 weeks
Other Name: Xarelto

Detailed Description:
This randomized II clinical trial enrolled patients with advanced upper gastrointestinal, hepatobiliary and pancreatic cancer who diagnosed venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis. Patients will be randomized in a 1:1 ratio and stratified by performance status (ECOG performance status 0-1 versus ≥2), type of cancer. The enrolled patients will receive either subcutaneous dalteparin using the CLOT regimen or to oral rivaroxaban using the conventional dosage given in the EINSTEIN trial 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.

Eligibility

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

Histologically or cytologically confirmed locally advanced unresectable or metastatic active cancer including esophageal cancer, gastroesophageal junctional cancer, gastric cancer, duodenal cancer, hepatocellular carcinoma, bile duct cancer, gall bladder cancer and 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, 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, massive iliofemoral deep vein thrombosis
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
Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03139487

Contacts
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
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
More Information

Responsible Party: Sook Ryun Park, Associated professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT03139487 History of Changes
Other Study ID Numbers: S2017-0331-0004
Study First Received: May 2, 2017
Last Updated: May 2, 2017
Individual Participant Data
Plan to Share IPD: Yes

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 Asan Medical Center:
Anticoagulant Adverse Reaction
Cancer-associated Thrombosis
Low molecular weight heparin
Direct oral anticoagulant

Additional relevant MeSH terms:
Pancreatic Neoplasms
Stomach Neoplasms
Thromboembolism
Esophageal Neoplasms
Thrombosis
Venous Thromboembolism
Duodenal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Stomach Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Head and Neck Neoplasms
Esophageal Diseases
Intestinal Neoplasms
Duodenal Diseases
Intestinal Diseases
Dalteparin
Heparin, Low-Molecular-Weight
Rivaroxaban
Anticoagulants
Fibrinolytic Agents

ClinicalTrials.gov processed this record on May 05, 2017