NCT03139487

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
176

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2017

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 2, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 4, 2017

Completed
3 months until next milestone

Study Start

First participant enrolled

August 7, 2017

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2021

Completed
Last Updated

January 6, 2020

Status Verified

January 1, 2020

Enrollment Period

4.2 years

First QC Date

May 2, 2017

Last Update Submit

January 2, 2020

Conditions

Cancer-associated ThrombosisEsophageal CancerStomach CancerHepatocellular CarcinomaPancreatic CancerDuodenal CancerEsophagogastric Junction CancerMalignant Gastrointestinal Stromal TumorAmpulla of Vater CancerBiliary Cancer (Cholangiocarcinoma, Gall Bladder Cancer)

Keywords

Anticoagulant Adverse ReactionCancer-associated ThrombosisLow molecular weight heparinDirect oral anticoagulant

Outcome Measures

Primary Outcomes (1)

  • Rate of clinical relevant bleeding

    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 Outcomes (7)

  • Rate of major bleeding

    6 months

  • Rate of total event of bleeding

    6 months

  • Time to major bleeding event

    6 months

  • Time to clinical relevant bleeding event

    6 months

  • Time to total event of bleeding

    6 months

  • +2 more secondary outcomes

Study Arms (2)

Low molecular weight heparin

ACTIVE COMPARATOR

Dalteparin, 200 IU/kg subcutaneously once daily for 4 weeks followed by 150 IU/kg once daily for 20 weeks

Drug: Dalteparin

Direct oral anticoagulant

EXPERIMENTAL

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: RivaroxabanDrug: apixaban

Interventions

RivaroxabanDRUG

15 mg q12 hours for 3 weeks followed by 20mg q24 hours for 21 weeks

Also known as: Xarelto
Direct oral anticoagulant
DalteparinDRUG

200 IU/kg q24 hours for 4 weeks followed by 150 IU/kg q24 hours for 20 weeks

Also known as: Fragmin
Low molecular weight heparin
apixabanDRUG

10 mg q12 hours for 7days followed by 5mg q12 hours for 21 weeks

Also known as: eliquis
Direct oral anticoagulant

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Asan Medical Center

Seoul, South Korea

RECRUITING

Related Publications (1)

  • Riaz IB, Fuentes HE, Naqvi SAA, He H, Sipra QR, Tafur AJ, Padranos L, Wysokinski WE, Marshall AL, Vandvik PO, Montori V, Bryce AH, Liu H, Badgett RG, Murad MH, McBane RD 2nd. Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis. Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041. Epub 2021 Jun 22.

    PMID: 34172290DERIVED

MeSH Terms

Conditions

Esophageal NeoplasmsStomach NeoplasmsCarcinoma, HepatocellularPancreatic NeoplasmsDuodenal NeoplasmsGastrointestinal Stromal TumorsBiliary Tract NeoplasmsCholangiocarcinomaGallbladder Neoplasms

Interventions

RivaroxabanDalteparinapixaban

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal DiseasesStomach DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeLiver NeoplasmsLiver DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System DiseasesIntestinal NeoplasmsDuodenal DiseasesIntestinal DiseasesNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueBiliary Tract DiseasesGallbladder Diseases

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsMorpholinesOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeparin, Low-Molecular-WeightHeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Central Study Contacts

Sook Ryun Park, M.D., Ph.D.

CONTACT

+82-2-3010-3210srpark@amc.seoul.kr

Seyoung Seo, M.D.

CONTACT

syseo@amc.seoul.kr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associated professor

Study Record Dates

First Submitted

May 2, 2017

First Posted

May 4, 2017

Study Start

August 7, 2017

Primary Completion

September 30, 2021

Study Completion

September 30, 2021

Last Updated

January 6, 2020

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Locations

KR(1)