Clinical Trial: A Phase II Study of Orally Administered BEZ235 Monotherapy in Patients With Metastatic or Unresectable Malignant PEComa

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Phase II Study of Orally Administered BEZ235 Monotherapy in Patients With Metastatic or Unresectable Malignant PEComa

Brief 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 mus

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Proportion of Patients with best Objective Response Rate (ORR) [ Time Frame: From treatment start to end of follow-up, assessed up to 30 months ]

Objective Response Rate is defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) according to RECIST. 1.1.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Progression Free Survival rate [ Time Frame: 32 weeks ]
    Time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
  • Duration of response [ Time Frame: From Initial response (CR or PR) until objective tumor progression, assessed up to 30 months ]
    Duration of response (DR) is measured from the time of initial response (CR or PR) until objective tumor progression.
  • Time to response [ Time Frame: From start of treatment to the initial response, assessed up to 30 months ]
    Time to response (TTR) is defined as time from treatment start until initial response (CR, PR)
  • Time to disease progression [ Time Frame: From start of treatment to first documented disease progression assessed up to 30 months ]
    Time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.
  • Overall survival [ Time Frame: From start of treatment to date of death (due to any cause) assessed up to 30 months ]
    Time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.
  • Number of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: up to 30 months ]
    The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by system organ class and or preferred term, severity (based on CTCAE grades), type of adverse event, relation to the study drug. Laboratory data will be graded according to CTCAE version 4.03 if relevant. For laboratory tests where grades are not defined according to CTCAE, abnormalities will be assessed according to laboratory normal ranges.


Original Secondary Outcome: Same as current

Information By: Novartis

Dates:
Date Received: September 6, 2012
Date Started: September 2012
Date Completion: January 2015
Last Updated: August 1, 2013
Last Verified: August 2013