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Malignant PEComa (Perivascular Epithelioid Cell Tumors)Phase 2NCT01690871

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

A Phase 2 study testing BEZ235 in people with Malignant PEComa (Perivascular Epithelioid Cell Tumors), run by Novartis Pharmaceuticals at 1 site in Spain.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BEZ235
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteSpain
Study dates
Sep 2012to Jan 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed diagnosis of malignant PEComa (included epithelioid AML) of primary disease or of metastatic lesion from archival tissue if it has been obtained within 12 months prior to enrollment in this study. This histological diagnosis includes immunochemistry as follows:
  • Immunohistochemically positive expression of a melanocytic marker (HMB45, MelanA or microphtalmia transcription factor) AND of a smooth muscle marker (smooth muscle actin, pan-muscle actin, h-caldesmon or calponin) is mandatory on primary or metastatic tumor biopsy.
  • Note: According to Folpe (2002), criteria for malignancy in non-AML PEComas are:
  • tumor size of more than 5 cm,
  • infiltrative growth pattern,
  • high nuclear grade,
Show all 19Show fewer
  • mitotic activity of more than 1/50 high power field (HPF),
  • necrosis,
  • vascular invasion
  • Thus, to be included in the trial, the patient should have tumor presenting with 2 or more criteria for malignancy associated with aggressive clinical behavior.
  • If the primary diagnosis was performed more than 12 months before enrollment, the histology of a primary/metastatic lesion should be reconfirmed with a fresh biopsy.
  • Availability of a representative tumor specimen, either archival or fresh tumor tissue for PI3K pathway analysis.
  • Unresectable/advanced and/or metastatic and documented progressive measurable disease as defined by RECIST 1.1 criteria. Prior to study entry, the progression of the disease should be confirmed by at least 2 sequential CT scans available for documentation (will be collected and hold).
  • Presence of measurable disease according to RECIST 1.1. Note: Lesions in previously irradiated areas can only be considered measurable if they have clearly progressed since the radiotherapy.
  • Treated with 1 or 2 prior lines of treatment Exclusion criteria
  • 1. Disease exclusions:
  • Lymphangioleiomyomatosis (LAM) exclusively
  • Active uncontrolled or symptomatic CNS metastases Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
  • Concurrent malignancy or malignancy in the last 3 years prior to start the study treatment (with the exception of adequately treated cervical carcinoma in situ or nonmelanoma skin cancer).

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Novartis Investigative Site

    Barcelona, Catalonia, 08025

Other trials in Spain

About this study

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

Read more

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.

Being tested
BEZ235
Keywords
Malignant PEComa, Angiomyolipoma, Tuberous Sclerosis Complex, Pi3kinase /m-tor inhibitors
Medical subject headings
Perivascular Epithelioid Cell Neoplasms, Angiomyolipoma, Tuberous Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BEZ235Drug

    Patients will be provided with an adequate supply of study treatment for self-administration at home. Unless otherwise warranted, new study drug packages will be provided to the patient at Cycle 1 Day 1 (start of treatment) and at Day 1 of each following treatment cycle. The first dose of BEZ235 (Cycle1 Day1) must be taken at the hospital.

Study groups in NCT01690871
Study groupRoleWhat they receive
BEZ235ExperimentalBEZ235 will be supplied in 200mg, 300mg and 400mg sachets packaged in boxes. Each box will contain only sachets of one strength.
Receives: Drug: BEZ235

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients with best Objective Response Rate (ORR)

    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.

    Measured: From treatment start to end of follow-up, assessed up to 30 months

Secondary outcomes (6)

  1. Progression Free Survival rate

    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.

    Measured: 32 weeks

  2. Duration of response

    Duration of response (DR) is measured from the time of initial response (CR or PR) until objective tumor progression.

    Measured: From Initial response (CR or PR) until objective tumor progression, assessed up to 30 months

  3. Time to response

    Time to response (TTR) is defined as time from treatment start until initial response (CR, PR)

    Measured: From start of treatment to the initial response, assessed up to 30 months

  4. Time to disease progression

    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.

    Measured: From start of treatment to first documented disease progression assessed up to 30 months

  5. Overall survival

    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.

    Measured: From start of treatment to date of death (due to any cause) assessed up to 30 months

  6. Number of Adverse Events as a Measure of Safety and Tolerability

    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.

    Measured: up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionJan 2015 (estimated)
  4. Study completionJan 2015 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01690871
Sponsor's protocol ID
CBEZ235ZIC01
Status last verified
Aug 2013
First submitted
6 Sep 2012
Last updated
2 Aug 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BEZ235 in people with Malignant PEComa (Perivascular Epithelioid Cell Tumors), run by Novartis Pharmaceuticals at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients with best Objective Response Rate (ORR) (time frame: From treatment start to end of follow-up, assessed up to 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01690871.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.

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