E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory multiple myeloma |
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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 |
Primary aim is to demonstrate that Sorafenib is active in patients with multiple myeloma in relapse or recurrent disease as a first evaluation of the effectiveness of this novel agent in the field of multiple myeloma. |
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E.2.2 | Secondary objectives of the trial |
To evaluate specific toxicity, safety, tolerability and response rates, duration of response as well as accompanying scientific topics like changes in blood vessel density and the prediction of clinical outcome and response to treatment by global gene expression profiling (GEP). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- informed consent - histologically or cytologically confirmed Multiple Myeloma in Stage IIA or IIIA (Durie and Salmon). - Measurable disease, definerd by: - Serum M protein at least 1.0 g/dl by protein electrophoreses or free light chain measurement an/or – - quantitative immunoglobulins and/or urinary M protein excretion of at least 200 mg/24 hours. - Relapse following any conventional multiple myeloma therapy (including autologous stem cell transplantation), or refractory to their most recent multiple myeloma therapy (including immunotherapy, radiation therapy, or other investigational agents). Note: Patients need not to have responded to the previous (one) therapeutic regimen. - Male or female patients > 18 years of age. - Life expectancy of at least 12 weeks - Patients must have an ECOG performance status of less or equal 2 - Women of childbearing age with a negative pregnancy test within 7 days prior to enrolment and willing to use adequate contraception during therapy - Men and women: Willing to use adequate contraceptive barrier methods during treatment. |
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E.4 | Principal exclusion criteria |
- Patients with non-secretory myeloma and plasma cell leukemia - Patients eligible and willing to undergo second-line high-dose therapy or ABSCT. - Hypercalcaemia >3.0 mmol/l (14 mg/dl) - Insufficient bone marrow, liver, and renal function as assessed by the following laboratory investigations at screening (Note: Values obtained within 7 days prior to the screening visit can be used): (Hemoglobin < 9.0 g/l, Absolute neutrophil count < 1.500/mm³, Platelets < 50.000/mm³, Total bilirubin > 1.5 x upper limit normal, ALT and AST > 2.5 x upper limit normal, Amylase and lipase > 1.5 x upper limit normal, Serum creatininie > 2.0 x upper limit normal, PT or INR and PTT > 1.5 x upper limit normal) - Major surgery within 4 weeks of enrolment - Patients with history of other malignancies during the past 5 years with the exception of adequately treated basal or squamous-cell skin cancer or cervical carcinoma or localized prostate carcinoma. - Systemic amyloidosis (except amyloidosis of skin or bone marrow). - Known history of HIV infection or chronic hepatitis B or C infection. - Active clinically serious bacterial or fungal infections (>or equal grade 2 NCI-CTCAE, Version 3.0). - Manifest depression - History of cardiac disease: congestive heart failure >NYHA class 2, active cardiovascular disease (MI more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring antiarrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. - Known neoplastic CNS abnormality - Known or suspected allergy to the investigational agent or any agent given in association with this trial. - Patients with seizure disorder requiring medication. - Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study. - Pregnant or breast feeding patients. - Concurrent anticancer chemotherapy or immunotherapy. (Note: The administration of bisphosphonates is recommended and not excluded). - Concurrent treatment with systemic corticosteroids. - Prior use of inhibitors of the Ras/Raf-, MEK-, AKT-kinase- and mTOR-signaling pathway or of farnesyl-transferase inhibitors. - Prior use of angiogenesis inhibitors (targeting VEGF/VEGFR, PDGF/PDGFR and other key molecules in angiogenesis). Note: the prior use of thalidmide and its derivatives is no exclusion criterium. - Concomitant Rifampicin and St. John´s Wort (hypericum perforatum). - Receiving immunotherapy, radiation therapy, or other investigational agents within 30 days prior to the first study drug administration.
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of progression free survival (PFS) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.1 | Randomised | No |
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) | No |
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 | 2 |
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 | 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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13 cycles a 28 days plus 12 months follow-up, after last patient in |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |