Gastrointestinal Stromal TumorsPhase 3ENESTNCT00471328
Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
A Phase 3 study testing Nilotinib in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 35 sites in 13 countries.
Trial summary
The study evaluated the safety and efficacy of nilotinib versus current treatment in adults with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant to the first and second line treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 248 participants
- Where
- 35 sitesin 13 countries
- Study dates
- Mar 2007to Jun 2011
- Phase
- Phase 3
- 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
- Age ≥18 years
- Radiological confirmation of disease progression during imatinib and sunitinib therapy OR intolerance to imatinib and/or sunitinib
- At least one measurable site of disease on CT/MRI scan
- Physically fit even if not able to work
- Normal organ, electrolyte, and bone marrow function
- Patients whose tumors had progressed on the control arm and had crossed over to the nilotinib arm.
Show all 9Show fewer
- The study was stopped due to meeting the primary efficacy endpoint of PFS at the interim analysis.
- Patients who were still being treated at the close of the Core study on the control arm or nilotinib arm (whose tumors have not progressed at the time of the end of the Core study).
- Patients must have had documented, confirmed stable, partial or complete response as defined by the RECIST criteria at the time of entry into the Extension study with the exception of patients who had progressed on the control arm.
Who cannot join
- Previous treatment with nilotinib or any other drug in this class or other targeted therapy
- Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks prior to study entry
- Impaired cardiac function
- Use of coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
- Women who are pregnant or lactating
- Use of other anticancer treatments or investigational drugs (with exception of the study drugs)
- Patients with a history of noncompliance with study drug treatment in the Core study protocol.
- Other protocol-defined inclusion/exclusion criteria applied
Trial locations and contacts
35 sites in 13 countries.
35 sites in 13 countries
United States11 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
University of Chicago Hospital
Chicago, Illinois, 60637
Wayne State University/Wertz Clinical Cancer Center
Detroit, Michigan, 48201
University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030-4009
UCLA's Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
St. Vincent's Comprehensive Cancer Center
New York, New York, 10011
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Washington Hospital Center - Washington Cancer Institute
Washington D.C., District of Columbia, 20010-2965
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157-1082
Germany9 sites
Novartis Investigative Site
Berlin
Novartis Investigative Site
Cologne
Novartis Investigative Site
Düsseldorf
Novartis Investigative Site
Essen
Novartis Investigative Site
Frankfurt
Novartis Investigative Site
Hanover
Novartis Investigative Site
Mannheim
Novartis Investigative Site
München
Novartis Investigative Site
Tübingen
France3 sites
Novartis Investigative Site
Bordeaux
Novartis Investigative Site
Lyon
Novartis Investigative Site
Marseille
Australia2 sites
Novartis Investigative Site
Auchenflower, Queensland, 4066
Novartis Investigative Site
East Melbourne, Victoria, 3002
Italy2 sites
Novrtis Investigative Site
Bologna
Novartis Investigative Site
Milan
About this study
Official title: A Randomized, Open-label, Multi-center Study to Evaluate the Efficacy of Nilotinib Versus Best Supportive Care With or Without a Tyrosine Kinase Inhibitor (Investigator's Choice) in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Both Imatinib and Sunitinib
The study evaluated the safety and efficacy of nilotinib versus current treatment in adults with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant to the first and second line treatments.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Nilotinib, Best Supportive Care (BSC) +/- imatinib or sunitinib
- Keywords
- GIST, adults, imatinib resistant, sunitinib resistant, AMN107, nilotinib, treatment, Gastrointestinal stromal tumor (GIST)
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called AMN107, Tasigna®
Nilotinib 400 mg twice daily (bid)
Best Supportive Care (BSC) +/- imatinib or sunitinibOther
Can include pain medication, localized radiotherapy, nutritional support, and/or oxygen therapy and blood transfusions. Imatinib or sunitinib can be administered at the last tolerated dose and regimen or at the Investigator's choice.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | 400mg twice daily in core and extension phases of the study. Receives: Drug: Nilotinib |
| Control/cross-over to Nilotinib | Active comparator | In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression. Receives: Drug: Nilotinib; Other: Best Supportive Care (BSC) +/- imatinib or sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Measured: Up to 16 months
Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
PFS is defined as the time from the first date of cross-over to nilotinib therapy from the control arm to the date of the first observation of documented disease progression. Tumor assessment was based on the local investigator's measurement using Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Measured: Up to 34 months
Secondary outcomes (7)
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, survival will be censored at the date of last contact.
Measured: Up to 16 months
Overall Survival During Core and Extension Phases of the Study
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, survival will be censored at the date of last contact. This analysis included both Core and Extension data as well as survival follow up data.
Measured: Up to 50 months (including core, extension and follow up period)
Overall Survival for Treatment Crossover Analysis Set
For patients who crossed-over to nilotinib from the control arm, the overall survival was the time from the first dose date of nilotinib after switching from control arm to the date of death due to any cause. If death was not observed, the OS was censored at the latest date the patient was known to be alive.
Measured: Up to 34 months
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Central Radiology Review During Primary Analysis (Data Cut-off: June, 2008)
The best overall response is the best response recorded from randomization until disease progression. The CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
Measured: Up to 16 months
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
The best overall response (CR/PR) must be confirmed by at least two determinations at least 4 weeks apart before progression. Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
Measured: Up to 34 months
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
The overall clinical benefit includes the best overall responses of CR, PR, or SD. The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
Measured: Up to 16 months
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
The overall clinical benefit includes the best overall responses of CR, PR, or SD. The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
Measured: Up to 34 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2007 (estimated)
- Study startMar 2007
- Primary completionAug 2008
- Study completionJun 2011
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.
- Other trials for Gastrointestinal Stromal TumorsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 248 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
- NCT00471328
- Sponsor's protocol ID
- CAMN107A2201
- Other IDs
- 2006-002267-11
- Acronym
- ENEST
- Status last verified
- Jun 2012
- First submitted
- 26 Apr 2007
- Last updated
- 12 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Multi-center Study to Evaluate the Efficacy of Nilotinib Versus Best Supportive Care With or Without a Tyrosine Kinase Inhibitor (Investigator's Choice) in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Both Imatinib and Sunitinib
- ClinicalTrials.gov ID
- NCT00471328
- Acronym / sponsor ID
- ENEST / CAMN107A2201
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- GIST, adults, imatinib resistant, sunitinib resistant, AMN107, nilotinib, treatment, Gastrointestinal stromal tumor (GIST)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 248 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- Aug 2008 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 9 May 2007 (estimated)
- Results
- Posted 17 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study evaluated the safety and efficacy of nilotinib versus current treatment in adults with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant to the first and second line treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: Nilotinib400mg twice daily in core and extension phases of the study. |
| Control/cross-over to Nilotinib | Active comparator | Drug: Nilotinib, Other: Best Supportive Care (BSC) +/- imatinib or sunitinibIn core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm. Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥18 years
- Radiological confirmation of disease progression during imatinib and sunitinib therapy OR intolerance to imatinib and/or sunitinib
- At least one measurable site of disease on CT/MRI scan
- Physically fit even if not able to work
- Normal organ, electrolyte, and bone marrow function
Key exclusion criteria (8 listed)
- Previous treatment with nilotinib or any other drug in this class or other targeted therapy
- Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks prior to study entry
- Impaired cardiac function
- Use of coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
- Women who are pregnant or lactating
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 |
|---|---|---|
| NilotinibAlso: AMN107, Tasigna®Nilotinib 400 mg twice daily (bid) | Drug | Control/cross-over to Nilotinib, Nilotinib |
| Best Supportive Care (BSC) +/- imatinib or sunitinibCan include pain medication, localized radiotherapy, nutritional support, and/or oxygen therapy and blood transfusions. Imatinib or sunitinib can be administered at the last tolerated dose and regimen or at the Investigator's choice. | Other | Control/cross-over to Nilotinib |
Primary outcome
Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
Time frame: Up to 16 months
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time frame: Up to 34 months
PFS is defined as the time from the first date of cross-over to nilotinib therapy from the control arm to the date of the first observation of documented disease progression. Tumor assessment was based on the local investigator's measurement using Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
7 secondary outcomes
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
Time frame: Up to 16 months
Overall Survival During Core and Extension Phases of the Study
Time frame: Up to 50 months (including core, extension and follow up period)
Overall Survival for Treatment Crossover Analysis Set
Time frame: Up to 34 months
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Central Radiology Review During Primary Analysis (Data Cut-off: June, 2008)
Time frame: Up to 16 months
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time frame: Up to 34 months
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
Time frame: Up to 16 months
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time frame: Up to 34 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
35 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nilotinib in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 35 sites in 13 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 9 inclusion and 8 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 12 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Germany, France, Australia, Italy and 8 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 May 2011). 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) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008) (time frame: Up to 16 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jun 2012.