A Phase II Study of Orally Administered BEZ235 Monotherapy in Patients With Metastatic or Unresectable Malignant PEComa
Status:
Withdrawn
Trial end date:
2015-01-01
Target enrollment:
Participant gender:
Summary
Study objectives:
The primary objective is to determine the efficacy of BEZ235 on Objective Response Rate (best
response on study) according to RECIST 1.1 criteria
The secondary objectives are:
- To determine the progression free survival rate at 32 weeks in the included population
- To assess the duration of response among responders
- To evaluate time to response
- To evaluate the time to progression
- To assess the overall survival
- To evaluate safety and tolerability of BEZ235
The exploratory objectives are:
- To identify molecular and genomic profiles of PEComas and their potential relationship
to clinical outcome by analyzing PIK3CA, Ras, Raf, TSC, AKT and PTEN alteration in tumor
samples (archival or fresh pre-treatment tumor biopsy) and PIK3CA in circulating DNA.
- To determine biomarkers relevant to BEZ235 activity by analyzing the expression of
phosphoproteins p-AKT, p-S6, p-4EBP1 at screening and during treatment as well as
biomarkers for the proliferation (Ki-67) and apoptosis (PARP) (only if fresh tissue
(optional) is available).
Study population:
The patient population consists of patients 18 years old or older with progressive
unresectable/advanced or metastatic malignant PEComas previously treated for
unresectable/advanced/metastatic disease with 1 to 2 prior lines of chemotherapy. Patients
must have adequate hematologic, renal, cardiac and hepatic functions and not be previously
treated with a mTOR inhibitor.
Number of patients:
16 to 33 patients
Overview of study design:
This is a prospective, multicenter, open-label, single arm, two-stage phase II study to
investigate the efficacy and tolerability of BEZ235 in patients with progressive metastatic
or unresectable/advanced malignant PEComas. The patient should have received 1 or 2 prior
lines of chemotherapy.
BEZ235 will be administered until disease progression. Sixteen patients will be enrolled into
Stage 1 and observed for at least 32 weeks at which time an interim analysis will be
performed (plus eventually 4-5 weeks for confirmation of responses occurring on or closely
before this cut-off date). If the number of patients with a response (CR or PR) is 2 or less,
the trial will be stopped for futility. If 3 or more patients experience a response
enrollment will continue up to 33 patients (Stage 2).
An Independent Data Monitoring Committee (IDMC) will be constituted for reviewing the interim
analysis.