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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00471328




Registration number
NCT00471328
Ethics application status
Date submitted
26/04/2007
Date registered
9/05/2007
Date last updated
12/06/2012

Titles & IDs
Public title
Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
Scientific 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
Secondary ID [1] 0 0
2006-002267-11
Secondary ID [2] 0 0
CAMN107A2201
Universal Trial Number (UTN)
Trial acronym
ENEST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Stromal Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nilotinib
Other interventions - Best Supportive Care (BSC) +/- imatinib or sunitinib

Experimental: Nilotinib - 400mg twice daily in core and extension phases of the study.

Active Comparator: Control/cross-over to Nilotinib - 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.


Treatment: Drugs: Nilotinib
Nilotinib 400 mg twice daily (bid)

Other interventions: Best Supportive Care (BSC) +/- imatinib or sunitinib
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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 16 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 34 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 16 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 50 months (including core, extension and follow up period)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 34 months
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Up to 16 months
Secondary outcome [5] 0 0
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).
Timepoint [5] 0 0
Up to 34 months
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to 16 months
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to 34 months

Eligibility
Key inclusion criteria
Inclusion criteria (Core Phase):

- 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

Inclusion criteria (Extension Phase):

- Patients whose tumors had progressed on the control arm and had crossed over to the
nilotinib arm.

- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria (Core Phase):

- 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

Exclusion criteria (Extension Phase):

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Auchenflower
Recruitment hospital [2] 0 0
Novartis Investigative Site - East Melbourne
Recruitment postcode(s) [1] 0 0
4066 - Auchenflower
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Canada
State/province [13] 0 0
Toronto
Country [14] 0 0
Czech Republic
State/province [14] 0 0
Praha 5
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux
Country [16] 0 0
France
State/province [16] 0 0
Lyon
Country [17] 0 0
France
State/province [17] 0 0
Marseille
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Duesseldorf
Country [20] 0 0
Germany
State/province [20] 0 0
Essen
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Koln
Country [24] 0 0
Germany
State/province [24] 0 0
Mannheim
Country [25] 0 0
Germany
State/province [25] 0 0
Muenchen
Country [26] 0 0
Germany
State/province [26] 0 0
Tubingen
Country [27] 0 0
Italy
State/province [27] 0 0
Bologna
Country [28] 0 0
Italy
State/province [28] 0 0
Milan
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seoul
Country [30] 0 0
Netherlands
State/province [30] 0 0
Leiden
Country [31] 0 0
Poland
State/province [31] 0 0
Warszawa
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Switzerland
State/province [33] 0 0
Chur

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00471328
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications