Pancreatic Neuroendocrine Tumors (pNET)Phase 2NCT01658436
BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
A Phase 2 study testing BEZ235 (Stage 1) in people with Pancreatic Neuroendocrine Tumors (pNET), run by Novartis Pharmaceuticals at 17 sites in 9 countries.
Trial summary
This is a Phase II study in 2 stages, evaluating BEZ235 plus best supportive care (BSC) versus placebo plus BSC in patients with advanced pancreatic neuroendocrine tumors (pNET) after failure of mTOR inhibitor therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neuroendocrine Tumors (pNET)
- What is being tested?
- BEZ235 (Stage 1)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 17 sitesin 9 countries
- Study dates
- Nov 2012to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Unresectable or metastatic, histologically confirmed low or intermediate grade pancreatic neuroendocrine tumor with radiological evidence of disease progression since last treatment
- Refractory disease to treatment with mTOR inhibitor
- Measurable disease per RECIST Version 1.1 using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
- Prior or concurrent therapy with SSA is permitted; a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment; SSA is not considered as a systemic treatment.
- WHO PS ≤ 1
- Adequate bone marrow function or organ function
Who cannot join
- Previous treatment with any PI3K or AKT inhibitor
- Discontinuation prior mTOR inhibitor therapy due to toxicity
- Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
- Radiotherapy, or major surgery within 4 weeks prior to study treatment start
- Hepatic artery embolization or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of study treatment start.
- More than 3 prior systemic treatment regimens (including cytotoxic chemotherapy, targeted therapy, immunotherapy)
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
United States4 sites
Dana Farber Cancer Institute GastrointestionalCancer Clinic
Boston, Massachusetts, 02215
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
Columbus, Ohio, 43210
Indiana University SC
Indianapolis, Indiana, 46202
Montefiore Medical Center SC-2
The Bronx, New York, 10467
Italy3 sites
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, Madrid, 28041
France2 sites
Novartis Investigative Site
Lyon, 69437
Novartis Investigative Site
Villejuif, 94805
About this study
Official title: A Multicenter, Two Stage, Phase II Study, Evaluating the Efficacy of Oral BEZ235 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in the Treatment of Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
This is a Phase II study in 2 stages, evaluating BEZ235 plus best supportive care (BSC) versus placebo plus BSC in patients with advanced pancreatic neuroendocrine tumors (pNET) after failure of mTOR inhibitor therapy.
Study design: This was a Phase II, two-stage, multicenter study, where Stage 1 was a single arm, open label design and Stage 2 was planned to be a randomized, double-blind study.
However, at the end of Stage 1, the futility was met and hence the Stage 2 was not initiated.
- Conditions
- Pancreatic Neuroendocrine Tumors (pNET)
- Being tested
- BEZ235 (Stage 1)
- Keywords
- advanced pancreatic neuroendocrine tumor, BEZ235, pNET
- Medical subject headings
- Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEZ235 (Stage 1)Drug
The investigational study drug used in this trial was BEZ235, which was supplied as 50mg, 200mg, 300mg, and 400mg solid dispersion sachets. Supply as 200mg and 50mg were provided for dose reduction. Patients were instructed to take the contents of one sachet of BEZ235 twice a day in the morning within 30 minutes after a light meal (breakfast).
| Study group | Role | What they receive |
|---|---|---|
| BEZ235 300 mg/400 mg bid (Stage 1) | Experimental | Stage 1 consisted of a single arm where patients received BEZ235 300mg or 400mg bid. Initially the study started with a dose of 400mg bid. However, following an amendment after the preliminary safety and tolerability data from the first 3 patients treated at the 400mg dose, the dosage was changed to 300mg bid. Receives: Drug: BEZ235 (Stage 1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review
PFS rate at 16 weeks was defined as a binary variable. Patients were considered as 'progression free' after 16 weeks if they had an overall lesion response of complete response (CR) partial response ('PR) or stable disease (SD)' and "progressed" if they had an overall lesion response of 'Progressive disease (PD) at the scan which occurred on day 105 after start of treatment, or later. Patients whose 16 weeks tumor assessment was unknown, missing or outside the window was not considered as 'progression free' and was considered a "failure" and counted only in the denominator for the estimation of the 16 week progression free rate.
Measured: 16 weeks after the first BEZ235 administration.
Secondary outcomes (2)
Stage 1- Overall Response Rate (ORR)
Overall Response rate was defined as the proportion of patients with a best overall response of complete response or partial response, based on investigator's assessment as per RECIST criteria version 1.1. Based on futility analysis conducted at the end of stage 1, stage 2 was not initiated.
Measured: Baseline, every 8 weeks up to 31 months
Stage 1 - Disease Control Rate
Disease control rate was defined as the proportion of patients with a best overall response of Complete Response, Partial response, or Stable disease, based on the investigator's assessment per RECIST version 1.1. Based on futility analysis conducted at the end of stage 1, stage 2 was not initiated.
Measured: Baseline, every 8 weeks up to 31 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study startNov 2012
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic Neuroendocrine Tumors (pNET)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01658436
- Sponsor's protocol ID
- CBEZ235F2201
- Other IDs
- 2012-000675-16
- Status last verified
- Apr 2016
- First submitted
- 6 Jul 2012
- Last updated
- 2 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Fazio N, Buzzoni R, Baudin E, Antonuzzo L, Hubner RA, Lahner H, DE Herder WW, Raderer M, Teule A, Capdevila J, Libutti SK, Kulke MH, Shah M, Dey D, Turri S, Aimone P, Massacesi C, Verslype C. A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. Anticancer Res. 2016 Feb;36(2):713-9.
PubMed 26851029
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Two Stage, Phase II Study, Evaluating the Efficacy of Oral BEZ235 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in the Treatment of Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
- ClinicalTrials.gov ID
- NCT01658436
- Acronym / sponsor ID
- CBEZ235F2201
- Conditions
- Pancreatic Neuroendocrine Tumors (pNET)
- Keywords
- advanced pancreatic neuroendocrine tumor, BEZ235, pNET
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 7 Aug 2012 (estimated)
- Results
- Posted 2 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II study in 2 stages, evaluating BEZ235 plus best supportive care (BSC) versus placebo plus BSC in patients with advanced pancreatic neuroendocrine tumors (pNET) after failure of mTOR inhibitor therapy.
Study design: This was a Phase II, two-stage, multicenter study, where Stage 1 was a single arm, open label design and Stage 2 was planned to be a randomized, double-blind study.
However, at the end of Stage 1, the futility was met and hence the Stage 2 was not initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BEZ235 300 mg/400 mg bid (Stage 1) | Experimental | Drug: BEZ235 (Stage 1)Stage 1 consisted of a single arm where patients received BEZ235 300mg or 400mg bid. Initially the study started with a dose of 400mg bid. However, following an amendment after the preliminary safety and tolerability data from the first 3 patients treated at the 400mg dose, the dosage was changed to 300mg bid. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Unresectable or metastatic, histologically confirmed low or intermediate grade pancreatic neuroendocrine tumor with radiological evidence of disease progression since last treatment
- Refractory disease to treatment with mTOR inhibitor
- Measurable disease per RECIST Version 1.1 using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
- Prior or concurrent therapy with SSA is permitted; a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment; SSA is not considered as a systemic treatment.
- WHO PS ≤ 1
Key exclusion criteria (6 listed)
- Previous treatment with any PI3K or AKT inhibitor
- Discontinuation prior mTOR inhibitor therapy due to toxicity
- Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
- Radiotherapy, or major surgery within 4 weeks prior to study treatment start
- Hepatic artery embolization or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of study treatment start.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BEZ235 (Stage 1)The investigational study drug used in this trial was BEZ235, which was supplied as 50mg, 200mg, 300mg, and 400mg solid dispersion sachets. Supply as 200mg and 50mg were provided for dose reduction. Patients were instructed to take the contents of one sachet of BEZ235 twice a day in the morning within 30 minutes after a light meal (breakfast). | Drug | BEZ235 300 mg/400 mg bid (Stage 1) |
Primary outcome
Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review
Time frame: 16 weeks after the first BEZ235 administration.
PFS rate at 16 weeks was defined as a binary variable. Patients were considered as 'progression free' after 16 weeks if they had an overall lesion response of complete response (CR) partial response ('PR) or stable disease (SD)' and "progressed" if they had an overall lesion response of 'Progressive disease (PD) at the scan which occurred on day 105 after start of treatment, or later. Patients whose 16 weeks tumor assessment was unknown, missing or outside the window was not considered as 'progression free' and was considered a "failure" and counted only in the denominator for the estimation of the 16 week progression free rate.
2 secondary outcomes
Stage 1- Overall Response Rate (ORR)
Time frame: Baseline, every 8 weeks up to 31 months
Stage 1 - Disease Control Rate
Time frame: Baseline, every 8 weeks up to 31 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26851029Fazio N, Buzzoni R, Baudin E, Antonuzzo L, Hubner RA, Lahner H, DE Herder WW, Raderer M, Teule A, Capdevila J, Libutti SK, Kulke MH, Shah M, Dey D, Turri S, Aimone P, Massacesi C, Verslype C. A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. Anticancer Res. 2016 Feb;36(2):713-9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BEZ235 (Stage 1) in people with Pancreatic Neuroendocrine Tumors (pNET), run by Novartis Pharmaceuticals at 17 sites in 9 countries.
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 6 inclusion and 6 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: finished, as of the sponsor's last update on 2 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Italy, Spain, France, Austria and 4 more countries. 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?
Yes. Results are posted in the registry (first posted 2 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review (time frame: 16 weeks after the first BEZ235 administration.). 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 NCT01658436, which also lists 1 linked publication.
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 May 2016.