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

NCT01856101 | Terminated Phase 2

• 3 other identifiers: UCL-ONCO2012-012012-004123-20CBEZ235ZBE01T
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 12

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.

Conditions

Carcinoma Transitional Cell

Keywords

TCC; Failure of platinum based chemotherapy

Outcome Measures

Primary Outcomes (1)

• Determine the efficacy of BEZ235 in patients with palliative TCC

  o Control disease rate at 16 weeks, including complete responses, partial responses and stable diseases according to RECIST criteria.

  at 16 weeks (radiological evaluation every 8 weeks)

Secondary Outcomes (1)

• 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

Study Arms (1)

BEZ235, powder

EXPERIMENTAL

* 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

Drug: BEZ235

Interventions

BEZ235 DRUG

The investigational study drug used in this trial is BEZ235, supplied as 200 mg, 300 mg and 400 mg sachets. BEZ235 is administered continuously twice-daily; complete cycle is 28 days. Starting dose is 300mg PO bid. At cycle 1 day 15, based on a clinical assessment, dose is adjusted for the rest of the study:• If no adverse event (AE) or only mild AE (G1) : the dose will be increase to 400 mg bid• If AE = G2 : the patient will continue at 300 mg bid • If G3 AE or higher : BEZ235 will be interrupt until resolved to ≤ G1 then reduce dose to 200 mg bid

Also known as: BEZ235 is a potent dual pan class I PI3K and mTOR inhibitor.

BEZ235, powder

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically- or cytologically-confirmed locally advanced or metastatic TCC not amenable to curative surgery or radiation.
• Documented disease progression (according RECIST 1.1 criteria) after first line platinum-based therapy (given in neoadjuvant/adjuvant or palliative setting).
• An interval of \>4 weeks since last anticancer treatment.
• 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.
• At least one measurable lesion by MRI or CT-scan
• ECOG performance status 0-1, in stable medical condition
• 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%.
• Patients must be over 18 years old and able to give written informed consent.
• Signed informed consent prior to beginning protocol specific procedure

You may not qualify if:

• Non- TCC bladder cancer
• More than 2 prior chemotherapy regimens given for palliation.
• 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)
• Patient with active uncontrolled or symptomatic central nervous system (CNS metastases).
• 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.
• Other uncontrolled medical condition (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes …)
• Other concomitant anticancer therapy.
• Previous therapy with PI3K and/or mTOR inhibitors (sirolimus, temsirolimus, everolimus)
• 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
• Pregnancy or risk of pregnancy.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead
• Novartis: collaborator

Study Sites (12)

Clinique Saint-Pierre à Ottignies

Ottignies, Brabant Wallon, 1340, Belgium

Location

Epicura- RHMS Baudour

Baudour, Hainaut, 7331, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, Hainaut, 6000, Belgium

Location

Hôpital de Jolimont

Haine-Saint-Paul, Hainaut, 7100, Belgium

Location

Centre Hospitalier Wallonie Picarde

Tournai, Hainaut, 7500, Belgium

Location

CHU de Liège site du Sart Tilman

Liège, Liège, 4000, Belgium

Location

Clinique du Sud Luxembourg

Arlon, Luxembourg, 6700, Belgium

Location

CHU de Mont-Godinne

Yvoir, Namur, 5530, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Clinique et Maternité Ste Elisabeth

Namur, 5000, Belgium

Location

Centre Hospitalier de Luxembourg

Luxembourg, Grand-Duché de Luxembourg, 1210, Luxembourg

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

dactolisib; Sirolimus

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Jean-Pascal Machiels, MD, PhD

  Centre du Cancer, Cliniques universitaires Saint-Luc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: May 17, 2013
• Study Start: February 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 10, 2019

Record last verified: 2019-04

Locations

LU (1); BE (11)