Pancreatic Neuroendocrine Tumors (pNET)Phase 2NCT01628913
Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors
A Phase 2 study testing BEZ235 and Everolimus in people with Pancreatic Neuroendocrine Tumors (pNET), run by Novartis Pharmaceuticals at 26 sites in 8 countries.
Trial summary
This was a multicenter, open label, randomized phase II study to evaluate the efficacy and safety of BEZ235 as compared to everolimus in patients with advanced, low to intermediate grade pancreatic neuroendocrine tumor (pNET). 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 and Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 26 sitesin 8 countries
- Study dates
- Oct 2012to Sep 2014
- 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
- Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor
- Progressive disease within the last 12 months
- Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT
Who cannot join
- Prior treatment with mTOR or PI3K inhibitors
- Patients with more than 2 prior systemic treatment regimens
- Previous cytotoxic chemotherapy, targeted therapy, or biotherapy within the last 4 weeks
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
26 sites in 8 countries.
26 sites in 8 countries
France5 sites
Novartis Investigative Site
Lyon, 69437
Novartis Investigative Site
Montpellier, 34298
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Reims, 51092
Novartis Investigative Site
Toulouse, 31054
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, Madrid, 28034
Novartis Investigative Site
Madrid, Madrid, 28046
Novartis Investigative Site
Seville, Andalusia, 41013
United Kingdom5 sites
Novartis Investigative Site
Glasgow, G11 6NT
Novartis Investigative Site
London, NW3 2QG
Novartis Investigative Site
London, SE1 9RT
Novartis Investigative Site
Manchester, M20 9BX
Novartis Investigative Site
Sheffield, S10 2SJ
United States4 sites
University of Colorado Univ Colorado
Aurora, Colorado, 80045
University of Kentucky Univ Kebtucky
Lexington, Kentucky, 40536-0098
Cedars Sinai Medical Center SC-3
Los Angeles, California, 90048
Montefiore Medical Center SC
The Bronx, New York, 10467
Italy3 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Pisa, PI, 56126
Novartis Investigative Site
Roma, RM, 00189
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1105 AZ
Novartis Investigative Site
Groningen, 9713 GZ
About this study
Official title: Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors
This was a multicenter, open label, randomized phase II study to evaluate the efficacy and safety of BEZ235 as compared to everolimus in patients with advanced, low to intermediate grade pancreatic neuroendocrine tumor (pNET).
Read the detailed description
Patients with advanced (unresectable or metastatic), low to intermediate grade (histologically confirmed well and moderately differentiated) pancreatic neuroendocrine tumor (pNET) were randomized to either BEZ235 or everolimus. The study was planned to include 140 patients, with 70 patients in the BEZ235 treatment group and 70 patients in the everolimus treatment group. An interim analysis was conducted on 62 randomized patients. The study was terminated as the BEZ235 treatment did not demonstrate a progression free survival advantage to everolimus treatment.
- Conditions
- Pancreatic Neuroendocrine Tumors (pNET)
- Being tested
- BEZ235, Everolimus
- Keywords
- Pancreatic, Neuroendocrine tumors, PNET, BEZ235, Everolimus
- Medical subject headings
- Neuroendocrine Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEZ235Drug
BEZ235 400 mg bid p.o. (by mouth, twice daily)
EverolimusDrug
Everolimus 10 mg qd p.o. (by mouth, daily)
| Study group | Role | What they receive |
|---|---|---|
| BEZ235 | Experimental | Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) Receives: Drug: BEZ235 |
| Everolimus | Active comparator | Patients received Everolimus 10 mg qd p.o. (by mouth, daily) Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions.
Measured: up to approx. 18 months
Secondary outcomes (3)
Objective Response Rate
Proportion of patients with a best overall response during the study of complete response (CR) or partial response (PR), based on the investigator assessment. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for all target and non-target lesions, as well as new lesions as assessed by CT or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of all target lesions; Overall Response (OR) = CR + PR.
Measured: up to approx. 18 months
Overall Survival (OS)
Time from randomization to the date of death due to any cause
Measured: up to approx. 30 months
Time to Treatment Failure (TTF)
Time from randomization to the date of the first of the following events:death due to any cause or progressive disease, treatment discontinuation due to toxicity or treatment discontinuation due to patient preference
Measured: up to approx. 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2012 (estimated)
- Study startOct 2012
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.
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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 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
- NCT01628913
- Sponsor's protocol ID
- CBEZ235Z2401
- Other IDs
- CBEZ235Z2401, 2012-000769-19
- Status last verified
- Mar 2016
- First submitted
- 25 Jun 2012
- Last updated
- 7 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Salazar R, Garcia-Carbonero R, Libutti SK, Hendifar AE, Custodio A, Guimbaud R, Lombard-Bohas C, Ricci S, Klumpen HJ, Capdevila J, Reed N, Walenkamp A, Grande E, Safina S, Meyer T, Kong O, Salomon H, Tavorath R, Yao JC. Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naive Advanced Pancreatic Neuroendocrine Tumors. Oncologist. 2018 Jul;23(7):766-e90. doi: 10.1634/theoncologist.2017-0144. Epub 2017 Dec 14.
PubMed 29242283
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT01628913
- Acronym / sponsor ID
- CBEZ235Z2401
- Conditions
- Pancreatic Neuroendocrine Tumors (pNET)
- Keywords
- Pancreatic, Neuroendocrine tumors, PNET, BEZ235, Everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 27 Jun 2012 (estimated)
- Results
- Posted 7 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, open label, randomized phase II study to evaluate the efficacy and safety of BEZ235 as compared to everolimus in patients with advanced, low to intermediate grade pancreatic neuroendocrine tumor (pNET).
Detailed description
Patients with advanced (unresectable or metastatic), low to intermediate grade (histologically confirmed well and moderately differentiated) pancreatic neuroendocrine tumor (pNET) were randomized to either BEZ235 or everolimus. The study was planned to include 140 patients, with 70 patients in the BEZ235 treatment group and 70 patients in the everolimus treatment group. An interim analysis was conducted on 62 randomized patients. The study was terminated as the BEZ235 treatment did not demonstrate a progression free survival advantage to everolimus treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BEZ235 | Experimental | Drug: BEZ235Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) |
| Everolimus | Active comparator | Drug: EverolimusPatients received Everolimus 10 mg qd p.o. (by mouth, daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor
- Progressive disease within the last 12 months
- Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT
Key exclusion criteria (4 listed)
- Prior treatment with mTOR or PI3K inhibitors
- Patients with more than 2 prior systemic treatment regimens
- Previous cytotoxic chemotherapy, targeted therapy, or biotherapy within the last 4 weeks
- Other protocol-defined inclusion/exclusion criteria may apply
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 |
|---|---|---|
| BEZ235BEZ235 400 mg bid p.o. (by mouth, twice daily) | Drug | BEZ235 |
| EverolimusEverolimus 10 mg qd p.o. (by mouth, daily) | Drug | Everolimus |
Primary outcome
Progression Free Survival (PFS)
Time frame: up to approx. 18 months
PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions.
3 secondary outcomes
Objective Response Rate
Time frame: up to approx. 18 months
Overall Survival (OS)
Time frame: up to approx. 30 months
Time to Treatment Failure (TTF)
Time frame: up to approx. 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29242283Salazar R, Garcia-Carbonero R, Libutti SK, Hendifar AE, Custodio A, Guimbaud R, Lombard-Bohas C, Ricci S, Klumpen HJ, Capdevila J, Reed N, Walenkamp A, Grande E, Safina S, Meyer T, Kong O, Salomon H, Tavorath R, Yao JC. Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naive Advanced Pancreatic Neuroendocrine Tumors. Oncologist. 2018 Jul;23(7):766-e90. doi: 10.1634/theoncologist.2017-0144. Epub 2017 Dec 14.
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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
26 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BEZ235 and Everolimus in people with Pancreatic Neuroendocrine Tumors (pNET), run by Novartis Pharmaceuticals at 26 sites in 8 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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 7 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in France, Spain, United Kingdom, United States, Italy and 3 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 7 Apr 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?
Progression Free Survival (PFS) (time frame: up to approx. 18 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 NCT01628913, 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 7 Apr 2016.