E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients affected by relapsed high-grade osteosarcoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031296 |
E.1.2 | Term | Osteosarcoma recurrent |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the antitumor activity of sorafenib 400 mg twice a day as second or third line treatment of relapsed high-grade osteosarcoma (not resectable, not resectable in a radical fashion, metastatic) |
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E.2.2 | Secondary objectives of the trial |
To explore sorafenib activity in this unfavourable OS subset. This will be accomplished by both recording overall survival, response rate (dimensional reduction), oncogene expression and activation. Any improvement in patients quality of life will be captured by the Pain and Analgesic scale. Finally, a specific effort will be conducted to evaluate the pattern of response, if any, given the peculiar patterns of response observed in solid tumors with molecular-targeted therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients with histologically documented and not surgically resectable or metastatic high-grade osteosarcoma which progressed after first or second line treatments for relapsing disease. 2) Measurable disease as defined by having at least one lesion that can be accurately measured by means of CT or MRI. Baseline evaluations must be completed within 2 weeks prior to enrollment. 3) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 and an estimated life expectancy of at least 3 months. Patients with and ECOG P.S. 2 are eligible if the P.S.2 depends solely on orthopedic problems. 4)Age >/= 15 years. 5)Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of treatment: -Hemoglobin > 9.0 g/dl; -Absolute neutrophil count (ANC)>1,500/mm3. -Platelet count >/=100,000/&#956;l. -Total bilirubin <1.5 times the ULN; -ALT and AST<2.5 x ULN(< 5 x ULN for patients with liver involvement of their cancer); -PT-INR/PTT <1.5xULN [Patients who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] -Serum creatinine < 1.5 x ULN. - Written informed consent |
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E.4 | Principal exclusion criteria |
1)Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. 2)Coexisting malignancies, except for basal or epithelial cell carcinoma of the skin or other solid tumors curatively treated with no evidence of disease for &#8805;3 years. 3)History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. 4)History of HIV infection or chronic hepatitis B or C. 5)Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 6)Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry) 7)Patients with seizure disorders requiring medication (such as steroids or anti-epileptics) 8)Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial. 9)Patients with evidence or history of bleeding diathesis. 10)Patients undergoing renal dialysis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients progression free at 4 months |
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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 | No |
E.6.4 | Safety | No |
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) | 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 | No |
E.8.1.2 | Open | No |
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) | 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 | 6 |
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
|
progressione, tossicita` intollerabile, evidenza cliniche che suggeriscono l`interruzione |
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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 | 0 |
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 | 0 |