A randomized, double-blind, placebo-controlled, multicenter phase III study to compare the safety and efficacy of RAD001 plus Best Supportive Care (BSC) versus BSC plus Placebo in patients with metastatic carcinoma of the kidney which has progressed on VEGF receptor tyrosine kinase inhibitor therapy.

Renal cell carcinoma (RCC) is expected to account for more than 35.000 new
diagnoses of cancer and over 12.000 cancer deaths in the United States during
2005. In Europe, the number of new diagnoses and cancer deaths from RCC is
approximately double that in the United States. In the Netherlands incidence of
RCC is 1500 per year. 1/3 has metastatic disease at time of diagnosis, 1/3 will
experience a relapse later on. Median survival for patients with metastatic
disease is about 13 months.

RCC is characterized by a high degree of resistance to chemotherapy. Interferon
Alfa and interleukin-2 are standard therapies for patients with metastatic RCC.
Only a minority of treated patients experiences a favorable response. Recently
developed VEGF targeted therapies have demonstrated activity in metastatic RCC.

There is no standard therapy available, once a patient's disease progresses
after VEGF targeted therapies. Therefore, the identification of new agents with
antitumor activity against RCC is of high priority.

To compare progression-free survival (PFS) in patients who receive RAD0901 plus
Best Supportive Care (BSC) versus patients who receive Matching Placebo plus
BSC.

After screening evaluations have been performed patients are randomized to
receive RAD001 plus BSC or BSC plus Matching Placebo. This part of the study is
the blinded treatment phase. Patients who have disease progression may be
unblinded, patients who had received placebo may be offered open-label
treatment with RAD001. This treatment may be continued till progressive disease
occurs. The patient will than enter the follow up phase.


Patients who have disease progression and are unblinded and had treatment with
RAD001 will enter the follow up phase immediately.

After randomisation patients will be instructed to use RAD001 10 mg daily dose
or matching placebo. Tablets contain 5 mg each.

After the screeningperiod patients have to visit the hospital once in 2 weeks.
Tumor evaluation will be done once in 2 months.
Pulmonary function tests will be done during the screeningperiod.
Use of RAD001 might cause side effects.

Na de screeningsperiode zal de patiënt 1 x per 2 weken naar het ziekenhuis
moeten voor controle.
Tumorcontrole zal 1 x per 2 maanden plaatsvinden.
Een longfunctietest is voor deelname in dit onderzoek nodig tijdens de
screeningsperiode.
Mogelijk risico gedurende dit onderzoek zijn de bijwerkingen van RAD001.