E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically- or cytologically-confirmed, metastatic, clear cell renal cell cancer RCC |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
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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 |
Aim of this study is to evaluate if the combination of Sorafenib 800 mg daily plus low-dose frequent interferon total weekly dose 15 MU has an increased antiangiogenic activity, and a consequent possible increased activity, than Sorafenib 800 mg daily plus interferon in the classic schedule total weekly dose 27 MU . Serum surrogate markers will be evaluated to eventually support clinical results of the study. |
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E.2.2 | Secondary objectives of the trial |
A pharmacoeconomic evaluation of the two treatment schedules Sorafenib same schedule and dosage, IFN total weekly dose 27 MU in Arm A vs 15 MU in ArmB will be performed. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Signed informed consent 2.Histologically or cytologically documented Clear Cell Renal Carcinoma RCC . In the case of a mixed histology the presence of a documented component of clear cell histology 61619; 50 is mandatory . Other variants are excluded 3.Prior Nephrectomy for primary site conservative approaches are allowed 4.In cases with initial diagnosis of RCC of more than 2 years RFS 2 years a histological/cytological confirmation of renal cell carcinoma origin of actual metastases is mandatory 5.Metastatic measurable disease at least one uni-dimensional measurable lesion by CT-scan or MRI according to RECIST criteria reported in Appendix 6.ECOG performance status 8804;2 ECOG scale reported in Appendix 7.Age 8805; 18 years 8.Life expectancy 8805; 3 months 9.Prior Surgery and/or Radiation Therapy to less or equal than 25 of the bone marrow are allowed. However, at least 4 weeks must have been elapsed since surgery or completion of radiation therapy and the patient must has recovered from side effects 10.ANC 8805;1.5 x 109/L; PLT 8805;100 x 109/L; Hb 8805;10 g/dl 11.Adequate hepatic function Total bilirubin 1.5 times the UNL ; ALT and AST 2.5 times the UNL 5 UNL in presence of liver metastases 12.Amylase and lipase 1.5 x the UNL 13.Serum creatinine 2.0 x the UNL 14.PT or INR and PTT 1.5 times the UNL Note patients who receive anti-coagulation treatment will be allowed to participate provided that no evidence of abnormality in these parameters exists 15.Patients must be accessible for treatment and follow up UNL upper normal limit of the institution. |
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E.4 | Principal exclusion criteria |
1.CNS metastases 2.Previous malignancy except for basal cell skin cancer and cervical carcinoma in situ adequately treated, or any other cancer from which the patient has been disease-free for 61619; 5 years 3.Any of the concomitant illness or medical condition indicated below Serious respiratory or cardiovascular disease such as congestive heart failure NYHA Class II -refer to Appendix- ; previous history within 6 months of myocardial infarction, angina pectoris or cardiac arrhythmias requiring anti-arrythmics excluding beta blockers or digoxin . Active coronary artery disease, uncontrolled hypertension 4.Unstable diabetes mellitus, significant neurological or psychiatric disorders or seizure disorder requiring medication such as anti-epileptics 5.Active clinically serious bacterial or fungal infections grade 2 NCI-CTC, Version 3 or active human immunodeficiency virus HIV infection or chronic hepatitis B or C 6.Previous treatment chemotherapy, Immunotherapy or experimental drugs for advanced disease adjuvant immnunotherapy could be allowed in the case of a relapse free survival 6 months 7.Prior isotope treatment e.g. strontium or samarium 8.Participation in clinical trials with other experimental agents within 30 days of study entry or concomitant treatment with other experimental drug 9.Concomitant treatment with bisphosphonates or any other anti-cancer therapy 10.Concomitant treatment with ketoconazole or itraconazole 11.Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial 12.History of organ allograft or autologous bone marrow transplant or stem cell rescue within four months of start of study drug 13.Prior use of Raf-kinase inhibitors RKI , MEK or Farnesyl transferase inhibitors 14.Known or suspected allergy to the investigational agent or any agent given in association with this trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-point of the study is to determine the Progression Free Survival PFS rates in the two 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Sorafenib 800 mg/die interferone alfa 2a 9MU TIW |
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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.8.5 | 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 | Information not present in EudraCT |
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |