Thromboembolism (VTE) in patients with active cancer MedDRA version: 15.1 Level: LLT Classification code 10066899 Term: Venous thromboembolism System Organ Class: 100000004866
Conditions
Interventions
Trade Name: Innohep®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TINZAPARIN SODIUM
CAS Number: 9041-08-1
Other descriptive name: Low Molecular Weight heparin(LMWH)
Concentration
Sponsors
LEO Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with a diagnosis of active cancer with a histologically or cytologically diagnosed solid tumour or haematological malignancy (evidence of early stage, regional or metastatic disease). Active cancer is defined as: • Patients diagnosed with cancer within the past 6 months, OR • Patients with recurrent, advanced or metastatic disease, OR • Patients that have received any treatment for cancer during the previous 6 months, OR • Patients not in complete remission of a chronic haematological malignancy. 2. Symptomatic and objectively confirmed acute proximal lower-limb DVT (anatomically including popliteal, femoral [superficial and common] and iliac [external and common]) and/or PE (located in segmental or larger pulmonary arteries) diagnosed within 72 hours prior to randomisation. Diagnosis of DVT/PE (at randomisation and at recurrence) must be made by appropriate objective imaging (see Section 10.7.3.4). 3. = 18 years of age or above the legal age of consent as per country specific regulations. 4. Patients with Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2 prior to the VTE episode. 5. Signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Life expectancy 180 mm Hg or diastolic blood pressure > 110 mm Hg). d. Recent intracranial haemorrhage (in the last 1 month prior to randomisation) which is at high risk of rebleeding and would prohibit anticoagulant therapy, according to the Investigator’s judgment. e. Recent (in the last 1 month prior to randomisation) brain, spinal or ophthalmic surgery. f. Thrombocytopenia (platelet count 1.5 x upper limit of normal (ULN) or equivalent to an aPTT ratio > 1.5 (if not receiving LMWH/ unfractionated heparin [UFH]). 5. Known hypersensitivity to the investigational product (Innohep®) or reference product (warfarin). 6. History of HIT. 7. Pre-randomisation therapeutic anticoagulant treatment for the current acute VTE administered for more than 72 hours prior to randomisation. 8. Patients that had been receiving therapeutic anticoagulation at the time of the VTE event (i.e. anticoagulant failure), using any anticoagulant, such as: a. Parenteral anticoagulants e.g. UFH, LMWH, fondaparinux, bivalirudin or hirudin. b. Vitamin K antagonist (VKA). c. New oral anticoagulants, e.g. dabigatran, rivaroxaban. Note: Chronic treatment with anti-platelet agents such as low dose of aspirin (up to 325 mg/day), clopidogrel or ticlopidine is allowed. 9. Patients unlikely to comply with the protocol, e.g. inability to return for study visits or inability to receive/administer daily SC injection. 10. Participation in another interventional study with active drug treatment or an investigational device. 11. Pregnant or breast-feeding women. Pregnancy status should be checked by serum or urine pregnancy testing prior to randomisation. 12. Women of childbearing potential not protected by an effective contraceptive method of birth control (as defined for contraception in the Informed Consent Form [ICF]) for the duration of the study. 13. Sexually active fertile men if they, or their partner (being a woman of childbearing potential), is not using effective birth control.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the efficacy of Innohep® in preventing the recurrence of Venous Thromboembolism(VTE) in patients with active cancer who have had an acute Venous Thromboembolism (VTE) episode. ;Secondary Objective: Secondary objectives are to: • Assess the safety of long-term Innohep®. • Identify clinical risk factors for recurrent Venous Thromboembolism (VTE) and major bleeding. • Assess overall mortality at 6 months. • Identify the possible role of coagulation parameters to predict recurrent Venous Thromboembolism (VTE) or prognosis. • Assess incidence and severity of post-thrombotic syndrome (PTS). • Assess health-related quality of life (QoL). • Assess healthcare resource utilisation.;Primary end point(s): The primary efficacy endpoint is a composite endpoint represented by the time in days from randomisation to the first occurrence of any of the following 5 objectively documented components • Symptomatic non-fatal DVTs. • Symptomatic non-fatal PEs. • Fatal PE. • Incidental proximal DVT (popliteal vein or higher). • Incidental proximal PE (segmental arteries or larger).;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint is a composite endpoint represented by the time in days from randomisation to the first occurrence of any of the following 5 objectively documented components: • Symptomatic non-fatal DVTs. • Symptomatic non-fatal PEs. • Fatal PE. • Incidental proximal DVT (popliteal vein or higher). • Incidental proximal PE (segmental arteries or larger). During the 6-month treatment period, scheduled visits will be performed to assess efficacy and safety. Final efficacy and survival assessments will be performed up until Day 180 (including 24 hours after last dose of study drug) or death, whichever comes first, for all patients (including patients who stop study drug prior to Day 180. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: Secondary efficacy endpoints are the time in days from randomisation to the first occurrence of: • The 5 individual components of the composite primary efficacy endpoint. • A composite endpoint of symptomatic DVT and/or PE, including fatal PE. Results from the central adjudication of events will be used for analysis. Safety endpoints: Safety endpoints will consist of major bleeding and clinically non-major bleeding, overall mortality, con-firmed HIT events, other thromboses, clinically significant abnormal laboratory data, clinically significant abnormal vital signs and all other AEs and SAEs. Bleeding will be defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria. Other endpoints: Other endpoints are coagulation biomarkers (e.g. D-dimer and tissue factor), PTS, health-related QoL, and healthcare resource utilisation.;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints are the time in days from randomisation to the first occurrence of: • The 5 individual components of the composite primary efficacy endpoint. • A composite endpoint of symptomatic DVT and/or PE, including fatal PE. Final assessments for other endpoints, including safety, healthcare resource utilisation, PTS and QoL will be performed up to 1 month (30 days) after the last dose of study drug taken (Post-Treatment Follow-Up visit). | — |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, Chile, Czech Republic, Denmark, Germany, Greece, Hong Kong, India, Israel, Italy, Korea, Republic of, Latvia, Mexico, Peru, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey
Contacts
Public ContactRegulatory Affairs
INC Research
Outcome results
None listed