To treat patients with histollogically- or cytologically-confirmed locally advanced or metastatic TCC not amenable to curative surgery or radiation.
Conditions
Interventions
Product Name: BEZ235
Product Code: BEZ235
Pharmaceutical Form: Powder for oral solution in sachet
CAS Number: 1028385-32-1
Current Sponsor code: BEZ235
Other descriptive name: BEZ235
Concentration uni
Sponsors
Centre du Cancer, Cliniques universitaires Saint-Luc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histollogically- 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 =65 years) yes F.1.3.1 Number of subjects for this age range 8 ;Inclusion criteria: 1. Patients with histollogically- 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 =65 years) yes F.1.3.1 Number of subjects for this age range 8 ;Inclusion criteria: 1. Patients with histollogically- 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 =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 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 metastases). 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, everolimus). 9. Concomittant 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. ;Exclusion criteria: 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 metastases). 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, everolimus). 9. Concomittant 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. ;Exclusion criteria: 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 metastases). 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, everolimus). 9. Concomittant 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy of BEZ235 in patients with palliative TCC in term of progression free survival rate (PFSR) at 16 weeks in one group of patients with PI3K/Akt/mTOR pathway deregulations and in one group of patients without PI3K/Akt/mTOR pathway deregulation;Secondary Objective: 1. Determine the safety profile of BEZ235 in patients with advanced TCC. 2. Determine the efficacy of BEZ235 in patients with TCCo Control disease rate at 16 weeks, including complete responses, partial responses and stable diseases according to RECIST criteria. o Duration of response, time to progression and overall survival.;Primary end point(s): Determine the efficacy of BEZ235 in patients with palliative TCC in term of progression free survival rate (PFSR) at 16 weeks in one group of patients with PI3K/Akt/mTOR pathway deregulations and in one group of patients without PI3K/Akt/mTOR pathway deregulation.;Timepoint(s) of evaluation of this end point: 16 weeks;Main Objective: Determine the efficacy of BEZ235 in patients with palliative TCC in term of progression free survival rate (PFSR) at 16 weeks in one group of patients with PI3K/Akt/mTOR pathway deregulations and in one group of patients without PI3K/Akt/mTOR pathway deregulation;Secondary Objective: 1. Determine the safety profile of BEZ235 in patients with advanced TCC. 2. Determine the efficacy of BEZ235 in patients with TCCo Control disease rate at 16 weeks, including complete responses, partial responses and stable diseases according to RECIST criteria. o Duration of response, time to progression and overall survival.;Primary end point(s): Determine the efficacy of BEZ235 in patients with palliative TCC in term of progression free survival rate (PFSR) at 16 weeks in one group of patients with PI3K/Akt/mTOR pathway deregulations and in one group of patients without PI3K/Akt/mTOR pathway deregulation.;Timepoint(s) of evaluation of this end point: 16 weeks;Main Objective: Determine the efficacy of BEZ235 in pati | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Few weeks after the inclusion a the patient. 2+3+4. At the end of the last cycle of the last patient included;Secondary end point(s): 1. Establish a possible correlation between BEZ235 efficacy and PI3K/Akt/mTOR pathway oncogenic deregulation, particularly but not exclusively PTEN loss and PIK3CA mutation(s). 2. Exploration of the angiogenesis related proteins detected on plasmatic samples collected before the treatment, during the treatment and at the progression disease. 3. Exploration of the proteins composing the mTOR pathway on pretreated tissue biopsy and in peripheral blood mononuclear cells (PBMC). 4. This translational research will be performed in the laboratory of Pharmacology and Therapeutics- Institute of Experimental and Clinical Research, Cliniques universitaires Saint Luc, Brussel;Timepoint(s) of evaluation of this end point: 1. Few weeks after the inclusion a the patient. 2+3+4. At the end of the last cycle of the last patient included;Secondary end point(s): 1. Establish a possible correlation between BEZ235 efficacy and PI3K/Akt/mTOR pathway oncogenic deregulation, particularly but not exclusively PTEN loss and PIK3CA mutation(s). 2. Exploration of the angiogenesis related proteins detected on plasmatic samples collected before the treatment, during the treatment and at the progression disease. 3. Exploration of the proteins composing the mTOR pathway on pretreated tissue biopsy and in peripheral blood mononuclear cells (PBMC). 4. This translational research will be performed in the laboratory of Pharmacology and Therapeutics- Institute of Experimental and Clinical Research, Cliniques universitaires Saint Luc, Brussel;Timepoint(s) of evaluation of this end point: 1. Few weeks after the inclusion a the patient. 2+3+4. At the end of the last cycle of the last patient included;Secondary end point(s): 1. Establish a possible correlation between BEZ235 efficacy and PI3K/Akt/mTOR pathway oncogenic deregul | — |
Countries
Belgium
Contacts
Public ContactLaboratoire d'Oncologie Médicale;Laboratoire d'Oncologie Médicale;Laboratoire d'Oncologie Médicale ;;
Centre du Cancer, Cliniques universitaires Saint-Luc;Centre du Cancer, Cliniques universitaires Saint-Luc;Centre du Cancer, Cliniques universitaires Saint-Luc
Outcome results
None listed