Efficacy and Safety of Bevacizumab/Temsirolimus Combination to Treat Advanced Renal Cell Carcinoma

Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Temsirolimus, After 1st Line Anti-VEGF Treatment in Patients With Advanced Renal Cancer

The purpose of this study is to determine whether the combination of bevacizumab/temsirolimus is effective in patients with advanced renal carcinoma progressing after anti-VEGF treatment

Inclusion Criteria:

• Adult patients (18th year of age completed)

• Signed and dated written informed consent form prior to any procedures related to this protocol.

• Histologically confirmed advanced clear cell renal cancer.

• Measurable disease.

• Failure of first line anti-VEGF treatment.

• Performance status 0-2, according to Eastern Cooperative Oncology Group (ECOG) .

• Satisfactory hematological parameters:

  • White blood cell count > 4000 mm3.
  • Platelet count 100000/mm3.
  • Neutrophil blood cell count > 1200/ mm3 .
  • Hemoglobin > 9,0 g/dL (can be achieved with red blood cell transfusion).

• Satisfactory biochemical parameters:

  • Serum creatinine < 2 x Upper Limit of Normal(ULN)
  • Aspartate Aminotransferase (AST)<2,5 x ULN
  • Alanine Transaminase (ALT)< 2,5 x ULN.
  • Bilirubin <2 x ULN

• (For female patients) Absence of pregnancy (negative pregnancy test for women of reproductive age before enrollment).

• (For female patients) Non-lactating women.

• Use of efficient contraceptive measures (women and men) to prevent possible pregnancy of female patient or female partner of a male patient during treatment and until 6 months after the end of treatment.

Exclusion Criteria:

• Prior treatment with mTOR inhibitor.
• Major surgery (including open biopsy) or insufficient recovery or existence of major trauma within 4 weeks before enrollment.
• Uncontrolled hypertension.
• Active infection requiring systemic treatment within 4 weeks prior to enrollment.
• Minor surgery (for instance, catheter placement) within 2 days before enrollment.
• Scheduled major surgery within the treatment period.
• Medical history in the last 6 months prior to enrollment of significant cardiovascular disease, diabetes, cardiac infarction, unstable angina, uncontrolled arrhythmia or significant heart failure.
• Indications of uncontrolled metastases or disease progression in CNS lesions (the suspicion of uncontrolled metastases or disease progression should be eliminated by imaging techniques within 14 days prior to enrollment).
• Medical history in the last 5 years prior to enrollment of any other malignancies (excluding the basal or squamous skin cell carcinoma or in situ carcinoma of the cervix).
• History of non-healing wound including active gastric ulcer.
• History of fistula in the last 6 months prior to enrollment.
• History of gastrointestinal perforations.
• Patient incapacity (for psychiatric or social reasons) to conform with the protocol.
• History of hemorrhagic predisposition.
• History of hypersensitivity to the medications under investigation.
• Significant proteinurea.
• Prior immunotherapy within 4 weeks prior to enrollment.
• Prior radiation treatment within 2 weeks prior to enrollment.
• Concomitant medication with inducers or strong inhibitors of the coenzyme CYP3A4 (see Appendix 5 for an indicative list of active compounds).
• Concurrent participation in other interventional clinical trials with investigational medicinal products.
• History of chronic interstitial lung disease.