Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Gastrointestinal Stromal Tumors
Interventions:	Drug: Nilotinib Other: Best Supportive Care (BSC) +/- imatinib or sunitinib

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients ongoing on treatment at primary analysis had option to enter extension. Patients in control arm were allowed cross over to Nilotinib arm at disease progression and considered as part of extension. Patients entering the extension part on control arm were permitted to cross over to the nilotinib only upon documented disease progression.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
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.

Description

Nilotinib

400 mg was taken orally twice daily in core and extension phase of the study

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.

Participant Flow for 2 periods

Period 1: Core Phase

	Nilotinib	Control/Cross Over to Nilotinib
STARTED	165	83
Crossover to Nilotinib:Started Extension	0	53
COMPLETED	58 ^[1]	16 ^[2]
NOT COMPLETED	107	67
Adverse Event	18	6
Death	8	4
Withdrawal by Subject	2	2
Abnormal laboratory value	1	0
Disease Progression	78	53
Administrative Problem	0	1
Protocol Deviation	0	1

[1]	Ongoing on treatment during completion of core.
[2]	Ongoing on treatment during completion of core

Period 2: Extension Phase

	Nilotinib	Control/Cross Over to Nilotinib
STARTED	41 ^[1]	67
Started:CrossOver Before PrimaryAnalysis	0	53
Started:CrossOver After PrimaryAnalysis	0	4
Started:CrossOver During Extension	0	10
COMPLETED	0	0
NOT COMPLETED	41	67
Adverse Event	3	12
Withdrawal by Subject	0	2
Death	1	7
Protocol Deviation	3	1
Treatment duration as per protocol	0	1
Disease Progression	32	44
New cancer Therapy	1	0
Administrative Problem	1	0

[1]	Out of 58 ongoing patients, 17 patients had progression or died before they could enter extension

Baseline Characteristics

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Reporting Groups

	Description
Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
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.
Total	Total of all reporting groups

Description

Nilotinib

400 mg was taken orally twice daily in core and extension phase of the study

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.

Total

Total of all reporting groups

Baseline Measures

	Nilotinib	Control/Cross Over to Nilotinib	Total
Number of Participants [units: participants]	165	83	248
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	118	57	175
>=65 years	47	26	73
Age [units: years] Mean ± Standard Deviation	57.4 ± 12.69	58.6 ± 10.57	57.8 ± 12.01
Gender [units: participants]
Female	64	36	100
Male	101	47	148
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0	0	0
Asian	21	11	32
Native Hawaiian or Other Pacific Islander	2	0	2
Black or African American	2	4	6
White	134	67	201
More than one race	0	0	0
Unknown or Not Reported	6	1	7

Outcome Measures

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1. Primary:

Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008) [ Time Frame: Up to 16 months ]

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2. Primary:

Progression-free Survival (PFS) From Local Investigator’s Assessment Based on Treatment Crossover Analysis Set [ Time Frame: Up to 34 months ]

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3. Secondary:

Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008) [ Time Frame: Up to 16 months ]

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4. Secondary:

Overall Survival During Core and Extension Phases of the Study [ Time Frame: Up to 50 months (including core, extension and follow up period) ]

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5. Secondary:

Overall Survival for Treatment Crossover Analysis Set [ Time Frame: Up to 34 months ]

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6. Secondary:

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 ]

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7. Secondary:

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 ]

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8. Secondary:

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 ]

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9. Secondary:

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 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00471328 History of Changes
Obsolete Identifiers:	NCT00488150
Other Study ID Numbers:	CAMN107A2201, 2006-002267-11
Study First Received:	April 26, 2007
Results First Received:	January 12, 2011
Last Updated:	June 5, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Czech Republic: State Institute for Drug Control Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices South Korea: Korea Food and Drug Administration (KFDA) Italy: The Italian Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Spain: Ministry of Health and Consumption Switzerland: Swissmedic Taiwan: Department of Health United States: Food and Drug Administration

Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib (ENEST)