Study of BEZ235 as Monotherapy in Patients With Transitional Cell Carcinoma After Failure of Platinum Based Chemotherapy

Phase 2

Terminated

• Conditions: Carcinoma Transitional Cell
• Interventions: Drug: BEZ235

• Registration Number: NCT01856101
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-12-10
• Study Start: 2013-02
• Study First Submitted QC: 2013-05-14
• Study First Posted: 2013-05-17
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-08
• Last Update Posted: 2019-04-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 22

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BEZ235, powder	BEZ235	* Group 1: patients without PI3K pathway activation; no loss of PTEN and no activating PIK3CA mutation. * Group 2: patients with PI3K pathway activation as defined by PIK3CA mutation and/or PTEN loss

Primary Outcome Measures

Name	Time	Method
Determine the efficacy of BEZ235 in patients with palliative TCC	at 16 weeks (radiological evaluation every 8 weeks)	o Control disease rate at 16 weeks, including complete responses, partial responses and stable diseases according to RECIST criteria.

Secondary Outcome Measures

Name	Time	Method
Determine the safety profile of BEZ235 in patients with advanced TCC	participants will be followed for the duration of hospital stay, an expected average of 16 weeks	The patient will have an appointment with the investigator on day 15 of cycle 1 and every day 1 of each cycle.

Trial Locations

Locations (12)

Hôpital de Jolimont; 🇧🇪 Haine-Saint-Paul, Hainaut, Belgium

CHU de Mont-Godinne; 🇧🇪 Yvoir, Namur, Belgium

Grand Hôpital de Charleroi; 🇧🇪 Charleroi, Hainaut, Belgium

Clinique du Sud Luxembourg; 🇧🇪 Arlon, Luxembourg, Belgium

Epicura- RHMS Baudour; 🇧🇪 Baudour, Hainaut, Belgium

Cliniques universitaires Saint-Luc; 🇧🇪 Brussel, Belgium

Centre Hospitalier de Luxembourg; 🇱🇺 Luxembourg, Grand-Duché De Luxembourg, Luxembourg

Clinique Saint-Pierre à Ottignies; 🇧🇪 Ottignies, Brabant Wallon, Belgium

Centre Hospitalier Wallonie Picarde; 🇧🇪 Tournai, Hainaut, Belgium

CHU de Liège site du Sart Tilman; 🇧🇪 Liège 1, Liège, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Clinique et Maternité Ste Elisabeth; 🇧🇪 Namur, Belgium