“TWIST”. RANDOMIZED PROSPECTIVE PHASE II STUDY OF TEMSIROLIMUS WITH OR WITHOUT LOW-DOSE INTERFERON ALPHA IN METASTATIC NON-CLEAR RENAL CELL CARCINOMA: GOIRC STUDY 02/2008

INTERVENTION: Trade Name: ROFERON A Pharmaceutical Form: Solution for injection INN or Proposed INN: Interferon alfa‐2a Concentration unit: million IU million international units Concentration type: equal Concentration number: 3‐ Product Name: Temsirolimus Product Code: CCI‐779 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: temsirolimus CAS Number: 162635‐04‐3 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ CONDITION: Patients with advanced non‐clear Cell Renal Carcinoma. ; MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma ; MedDRA version: 9.1 Level: PT Classification code 10038458 Term: Renal granular cell carcinoma ; MedDRA version: 9.1 Level: PT Classification code 10038414 Term: Renal cell carcinoma stage IV PRIMARY OUTCOME: Main Objective: Progression Free Survival (PFS) Primary end point(s): Progression Free Survival (PFS) rates in the two arms. Secondary Objective: Overall Response Rate (RECIST Criteria); Time to Progression (TTP); Safety; Overall Survival (OS). INCLUSION CRITERIA: Signed informed consent Histologically or cytologically documented non‐clear Cell Renal Carcinoma (with centralized review of histological specimens). In the case of a mixed histology the presence of a documented component of clear cell histology <50% is mandatory. Urothelial upper urinary tract tumors are excluded. In cases with initial diagnosis of non‐clear RCC of more than 2 years (RFS >2 years) a histological/cytological confirmation of renal cell carcinoma origin of actual metastases is mandatory. Metastatic measurable disease (at least one uni‐dimensional measurable lesion by CT‐scan or MRI) according to RECIST criteria (reported in Appendix Karnofsky performance status (KPS) ≥ 70 (KPS scale reported in Appendix) Age ≥ 18 years§ Life expectancy ≥ 3 months 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