Clinical trial NCT01856101: Study of BEZ235 as Monotherapy in Patients With Transitional Cell Carcinoma After Failure of Platinum Based Chemotherapy
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma Transitional Cell
Keywords: TCC
Failure of platinum based chemotherapy
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2013-05-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The mTOR (mammalian Target of Rapamycin) protein is the center of the mTOR pathway that plays an important role in cell growth, proliferation, survival and angiogenesis through sensing and integrating energetic signals from cellular environment. The mTOR protein is composed of two complex, mTOR complex 1 (mTOR C1) and mTOR complex 2 (mTOR C2).

In regards of mTOR pathway dysregulations observed in TCC development, there is a rational to test BEZ23 in advanced TCC. BEZ235 is a pan-class I PI3K inhibitor that, in addition, binds to the catalytic site of mTOR, inhibiting mTOR C1 and mTOR C2.


Eligibility criteria: Inclusion Criteria:

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

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. 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.

Primary outcomes:
measure: Determine the efficacy of BEZ235 in patients with palliative TCC
timeFrame: at 16 weeks (radiological evaluation every 8 weeks)
Secondary outcomes:
measure: Determine the safety profile of BEZ235 in patients with advanced TCC
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 16 weeks
Other outcomes:
Locations:
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre à Ottignies
state: Brabant Wallon
city: Baudour
country: Belgium
facility: Epicura- RHMS Baudour
state: Hainaut
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
state: Hainaut
city: Haine-Saint-Paul
country: Belgium
facility: Hôpital de Jolimont
state: Hainaut
city: Tournai
country: Belgium
facility: Centre Hospitalier Wallonie Picarde
state: Hainaut
city: Liège 1
country: Belgium
facility: CHU de Liège site du Sart Tilman
state: Liège
city: Arlon
country: Belgium
facility: Clinique du Sud Luxembourg
state: Luxembourg
city: Yvoir
country: Belgium
facility: CHU de Mont-Godinne
state: Namur
city: Brussel
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Namur
country: Belgium
facility: Clinique et Maternité Ste Elisabeth
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
state: Grand-Duché De Luxembourg
Study officials:
affiliation: Centre du Cancer, Cliniques universitaires Saint-Luc
name: Jean-Pascal Machiels, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: