E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thromboembolism (VTE) in patients with active cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066899 |
E.1.2 | Term | Venous thromboembolism |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a diagnosis of active cancer with a histologically or cytologically diagnosed solid tumour (evidence of early stage, regionally advanced or metastatic disease) or haematological malignancy. Active cancer is defined as: • Patients diagnosed with cancer within the past 6 months, OR • Patients with recurrent, regionally 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 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 diagnosed within 72 hours prior to randomisation (the 72 hour count starts when the diagnosis is confirmed by imaging). Diagnosis of DVT/PE must be made by appropriate objective imaging 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. |
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E.4 | Principal exclusion criteria |
1. Life expectancy < 6 months. 2. Patients with basal cell carcinoma or non-melanoma skin cancer where this is their only cancer diagnosis. 3. Creatinine clearance ≤ 20 ml/min according to the abbreviated Modification of Diet in Renal Disease (aMDRD) formula (see Appendix V). 4. Contra-indications to anticoagulation: a. Active or recent (≤ 1 months) clinically significant bleeding, including gastrointestinal bleeding or peptic ulcer. b. History of bleeding disorder or coagulopathy (congenital, acquired or unexplained repeated bleeding episodes). c. Increased risk of bleeding due to tumour characteristics or other condition prohibiting the use of therapeutic anticoagulation according to the Investigator’s judgment. d. Uncontrolled arterial hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg). e. 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. f. Recent (in the last 1 month prior to randomisation) brain, spinal or ophthalmic surgery. g. Thrombocytopenia (platelet count < 50 x 109/ L). h. Coagulopathy due to liver insufficiency as indicated by a prolonged baseline activated partial thromboplastin time (aPTT) > 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 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.
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E.5 End points |
E.5.1 | 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).
Results from central adjudication of events will be used for analysis.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |