E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemo-naive hormone refractory prostate cancer |
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MedDRA Classification |
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 |
To estimate and compare the 12-week progression-free rate of BIBF 1120, BIBW 2992 or sequential administration of BIBF 1120 and BIBW 2992 in patients with HRPC as determined by radiographic, bone and PSA criteria. |
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E.2.2 | Secondary objectives of the trial |
To evaluate additional efficacy related endpoints (e.g. PSA response/progression, duration of PSA response, RECIST tumor progression rate, time to progression, overall objective response, overall survival) and safety related endpoints (e.g. incidence and intensity of adverse events, changes in safety laboratory parameters) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age >18 years. •Signed informed consent. •Able to comply with protocol requirements. •Histologically, cytologically or biochemically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following at least one hormonal therapy, which must include orchidectomy or gonadotropin releasing hormone agonist (GnRHa). •Progressive Disease (PD) is defined as a minimum of three consecutive serum PSA measurements obtained at least 7 days apart within the previous 3 months of start of trial, which document progressively increasing values. Patients with progression of measurable disease (RECIST) or progression of bone disease must also fit the criterion for PSA progression. •Patients must have documented progression (as defined above) following anti-androgen withdrawal of 4 weeks duration for flutamide and 6 weeks for bicalutamide or nilutamide. For a patient who has withdrawn from anti-androgen therapy less than 6 months prior to inclusion in trial one of the following criteria is also required: •Following the completion of the anti-androgen withdrawal period one PSA higher than the last pre-withdrawal PSA. Or •Following the completion of the anti-androgen withdrawal period if the PSA value has decreased, he can still qualify if 2 increases in PSA are documented after the post- withdrawal nadir. •PSA > 5ng/mL. •Life expectancy of at least 12 weeks. •ECOG performance status 0-1 •Stable analgesia requirements. •Adequate hepatic function: total bilirubin < 26µmol/L, ALT and/or AST < 1.5x upper limit of normal (ULN). •Adequate renal function: serum creatinine ≤1.5 x ULN. •INR Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of normal. •Absolute neutrophil count (ANC) ≥ 1.5 x109/l, Platelets ≥100 x 109/l. •Haemoglobin ≥ 9.0 g/dl. •LVEF ≥50 % on MUGA scan or echocardiogram. •Castrate testosterone level [< 20ng/dl or <0.69nM (nM/L x 28.8 = ng/dl)], which must be maintained during the duration of the trial by orchidectomy or medical castration. •Patient on oral or intravenous bisphosphonates are allowed to enter the trial as long as they have been on bisphosphonates for a minimum of 3 months.
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E.4 | Principal exclusion criteria |
•Prior treatment with inhibitors of EGFR, HER 2 and/or VEGF receptors. •Prior treatment with cytotoxic chemotherapy. •Known hypersensitivity to the trial drugs or their excipients. •Systemic corticosteroids 28 days before screening (inhaled corticosteroids prescribed for bronchospasm are allowed). Patients on long-term stable-dose steroids for concurrent illness are not excluded. •Treatment with any investigational drug within 28 days of trial onset. •History of other malignancies which could affect compliance with the protocol or interpretation of results within 5-years. Patients with adequately treated basal or squamous cell skin cancer are generally eligible. •Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the trial. •Major injuries and/or surgery within 4 weeks of trial onset or bone fracture and planned surgical procedures during the trial period. •Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure > NYHA II). •History of haemorrhagic or thrombotic event in the past 12 months. Known inherited predisposition to bleeds or to thrombosis. •Patient with history or clinical evidence of CNS disease or brain metastases. •Patients with symptoms of impending or established spinal cord compression. •Gastrointestinal disorders or abnormalities that would inhibit absorption of the trial drug. •Patients who require full-dose anticoagulation. •Radio- or immunotherapy within the past four weeks prior to treatment with the trial drug. •Patients unable to comply with the protocol. •Active alcohol or drug abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free rate (defined by a composite endpoint of absence of PSA, bone metastasis and RECIST progression) after 12 weeks of treatment in each of the treatment arms |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |