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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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)
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
Timepoint [2] 0 0
Up to 34 months
Secondary outcome [1] 0 0
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
Timepoint [1] 0 0
Up to 16 months
Secondary outcome [2] 0 0
Overall Survival During Core and Extension Phases of the Study
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
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)
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
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)
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
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
Sex
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.