Study in Non-Clear Cell Renal Carcinoma (Ncc-RCC) Temsirolimus Versus Sunitinib

Inclusion criteria

• Adult males and females: ≥18 years of age.
• Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
• Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated.
• PS 0-2 ECOG
• Signed written informed consent.
• White blood cell count (WBC) ≥4x10*9/L with neutrophils ≥1.5 x 10*9/L, platelet count ≥100x10*9/L, hemoglobin ≥9 g/dL.]
• Total bilirubin <2 x upper limit of normal.
• AST and ALT <2.5 x upper limit of normal, or <5 x upper limit of normal in case of liver metastases.
• Serum creatinine <2.0 x upper limit of normal.
• Normal ECG without QT prolongation (QTc < 450msec).
• Adequate cardiac function (left ventricular ejection fraction > 40% as assessed by ECHO.

Exclusion criteria

• Predominant clear-cell RCC
• Resectability or other curative options
• Any investigational drug within the 30 days before inclusion.
• Prior systemic treatment for their RCC.
• Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments.
• Radiotherapy within the last 4 weeks.
• Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
• Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial.
• Clinically symptomatic brain or meningeal metastasis. (known or suspected)
• Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers or digoxin).
• History of any of the following cardiac events within the past 6 months:

• myocardial infarction (including severe/unstable angina),
• coronary/peripheral artery bypass graft,
• congestive heart failure (CHF),
• cerebrovascular accident,
• transient ischemic attack,
• pulmonary embolism.
• No hemorrhage ≥ grade 3 within the past 4 weeks
• Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥3 anti-hypertensive drugs
• History of relevant pulmonary hypertension or interstitial lung disease.
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
• Previous malignancy (other than renal cancer cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor [Ta, Tis and T1].
• History of organ allograft
• Significant disease which, in the investigator's opinion would exclude the patient from the study
• Patients with seizure and epileptic disorder or other conditions requiring medication (such as phenytoin, carbamazepin, phenobarbital)
• Patients under strong inducers or inhibitors to CYP Isoenzymes
• Patients with hypersensitivity to the antihistamine or patients who cannot receive the antihistamine for other medical reasons
• Patients requiring long-term cortisone therapy
• Patients requiring oral anticoagulation treatment, such as marcoumar. (Anticoagulation treatment with heparin or low molecular weight heparin [LMWH] is allowed provided that close monitoring is performed).
• Surgery within at least 2 weeks prior to randomization
• HIV seropositivity.
• Abnormal pulmonary function (DLCO < 50%). [Pulmonary function tests need only to be performed if abnormal pulmonary function present in medical history].
• Poorly controlled diabetes mellitus.
• Liver cirrhosis, chronic hepatitis
• Legal incapacity or limited legal capacity
• Known alcohol or drug abuse.
• Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.