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

  • STATUS
    Recruiting
  • End date
    Sep 30, 2021
  • participants needed
    176
  • sponsor
    Asan Medical Center
Updated on 23 January 2021
thrombosis
renal function
cancer
carcinoma
anticoagulants
international normalized ratio
prothrombin
metastasis
liver metastasis
esophageal cancer
gastric cancer
thromboplastin
cancer chemotherapy
esophagus cancer
cholangiocarcinoma
pancreatic cancers
kidney function test

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.

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.

Details
Condition Pancreatic Cancer, Adenocarcinoma, Pancreatic disorder, Biliary neoplasm, Esophageal Diseases, Esophageal Cancer, HEPATIC NEOPLASM, Neoplasm of unspecified nature of digestive system, HEPATOCELLULAR CARCINOMA, Gastropathy, Gastric Cancer, head and neck cancer, Duodenal Cancer, Stomach Discomfort, Pancreatic Disorders, Esophageal Carcinoma, Ampullary Cancer, Ampullary Carcinoma, Gastric Carcinoma, Esophagogastric Junction Cancer, Ampulla of Vater Cancer, Cancer-associated Thrombosis, Hepatobiliary Cancer, Urothelial Tract Cancer, Islet Ce417ll Cancer, Esophageal Disorders, Liver Cancer, Malignant Adenoma, Stomach Cancer, Biliary Tract Cancer, Digestive System Neoplasms, Cancer-associated Thrombosis, Malignant Gastrointestinal Stromal Tumor, gastric cancers, esophagus cancer, oesophageal cancer, carcinoma of ampulla of vater, cancer of the pancreas, pancreatic cancers, cancer, pancreatic, liver cell carcinoma, cancer of the esophagus, oesophageal carcinoma, biliary cancer, Cancer-associated Thrombosis
Treatment Rivaroxaban, dalteparin, Apixaban
Clinical Study IdentifierNCT03139487
SponsorAsan Medical Center
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 80 yrs?
Gender: Male or Female
Do you have any of these conditions: Biliary neoplasm or HEPATOCELLULAR CARCINOMA or Malignant Gastrointestinal Stromal Tumor or Hepatobiliary Cancer or Pancreatic Cancer or Ampulla of Va...?
Do you have any of these conditions: Ampullary Carcinoma or Esophageal Carcinoma or oesophageal carcinoma or Esophagogastric Junction Cancer or Pancreatic Disorders or Malignant Gastroint...?
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
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