Efficacy and Safety of AMN107 Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00471328

Purpose

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.

Condition	Intervention	Phase
Gastrointestinal Stromal Tumors	Drug: AMN107 Other: Best Supportive Care (BSC) +/- imatinib or sunitinib	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: gastrointestinal stromal tumor

MedlinePlus related topics: Cancer

Drug Information available for: Imatinib Imatinib mesylate Sunitinib malate Sunitinib AMN 107

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression-free Survival (PFS) Based on Central Radiology Review [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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 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.

Secondary Outcome Measures:

Overall Survival [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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.
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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).
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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.

Enrollment:	248
Study Start Date:	March 2007
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AMN107 400mg twice daily	Drug: AMN107
Active Comparator: Best Supportive Care (BSC) +/- imatinib or sunitinib	Other: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

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

Exclusion criteria:

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

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471328

Show 35 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00471328 History of Changes
Other Study ID Numbers:	CAMN107A2201
Study First Received:	April 26, 2007
Results First Received:	January 12, 2011
Last Updated:	September 8, 2011
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 - French Health Products Safety Agency; 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

Keywords provided by Novartis:

GIST
adults
imatinib resistant
sunitinib resistant

AMN107
nilotinib
treatment
Gastrointestinal stromal tumor (GIST)

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Sunitinib
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012