A Single Arm, Multicenter, Phase II Study of BEZ235 as Monotherapy in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma (TCC) After Failure of Platinum Based Chemotherapy.
1. Patients with histologically- or cytologically-confirmed locally advanced or
metastatic TCC not amenable to curative surgery or radiation.
2. Documented disease progression (according RECIST 1.1 criteria) after first line
platinum-based therapy (given in neoadjuvant/adjuvant or palliative setting).
3. An interval of >4 weeks since last anticancer treatment.
4. Archival paraffin-embedded tumor tissue (block or at least 20 unstained slides) of
the primary tumor and/or metastases. The most recent archival tissue is mandatory.
Recidive of the disease should lead to perform if possible novel biopsies, as major
oncogenic differences are found between primary tumor and secondary lesions.
5. At least one measurable lesion by MRI or CT-scan
6. ECOG performance status 0-1, in stable medical condition
7. Patients must have adequate organ function: Hemoglobin ≥ 9 g/100 ml, neutrophils ≥
1,000/mm3, platelets ≥ 100,000/mm, INR ≤ 1.5, total serum bilirubin ≤ 1.5 x ULN,
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (or
<5.0 x ULN if hepatic metastases are present), creatinine £1.5 x ULN, fasting plasma
glucose <140mg/dl, HbA1c < 8%.
8. Patients must be over 18 years old and able to give written informed consent.
9. Signed informed consent prior to beginning protocol specific procedure
1. Non- TCC bladder cancer
2. More than 2 prior chemotherapy regimens given for palliation.
3. Concurrent malignancy or previous malignancy in the last 3 years prior to start the
study treatment (with the exception of a history of adequately treated cervical
carcinoma in situ or non-melanoma skin cancer)
4. Patient with active uncontrolled or symptomatic central nervous system (CNS
5. Significant active cardiac disease including uncontrolled high blood pressure,
unstable angina, congestive heart failure, myocardial infarction within the previous
6 months, or serious cardiac arrhythmias.
6. Other uncontrolled medical condition (active infections requiring antibiotics,
bleeding disorders, uncontrolled diabetes …)
7. Other concomitant anticancer therapy.
8. Previous therapy with PI3K and/or mTOR inhibitors (sirolimus, temsirolimus,
9. Concomitant drugs such as coumarin and warfarin, and drugs known to induce torsade de
pointe, drugs known to be moderate or strong inhibitors or inducers of CYP3A4
10. Pregnancy or risk of pregnancy.