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

NCT00471328 | Completed Phase 3 Results DMC

• 2 other identifiers: CAMN107A22012006-002267-11
• Study Type: interventional
• Target: 248
• Locations: 12 countries
• Sites: 34

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.

Conditions

Gastrointestinal Stromal Tumors

Keywords

GIST; adults; imatinib resistant; sunitinib resistant; AMN107; nilotinib; treatment; Gastrointestinal stromal tumor (GIST)

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 34 months

Secondary Outcomes (7)

• Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)

  Up to 16 months

• Overall Survival During Core and Extension Phases of the Study

  Up to 50 months (including core, extension and follow up period)

• Overall Survival for Treatment Crossover Analysis Set

  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)

  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

  Up to 34 months

Study Arms (2)

Nilotinib

EXPERIMENTAL

400mg twice daily in core and extension phases of the study.

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.

Drug: Nilotinib; Other: Best Supportive Care (BSC) +/- imatinib or sunitinib

Interventions

Nilotinib DRUG

Nilotinib 400 mg twice daily (bid)

Also known as: AMN107, Tasigna®

Control/cross-over to Nilotinib; Nilotinib

Best Supportive Care (BSC) +/- imatinib or sunitinib OTHER

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.

Control/cross-over to Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (35)

UCLA's Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Washington Hospital Center - Washington Cancer Institute

Washington D.C., District of Columbia, 20010-2965, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Wayne State University/Wertz Clinical Cancer Center

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

St. Vincent's Comprehensive Cancer Center

New York, New York, 10011, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157-1082, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

University of Texas/MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Auchenflower, Queensland, 4066, Australia

Location

Novartis Investigative Site

East Melbourne, Victoria, 3002, Australia

Location

Novartis Investigative Site

Vienna, Austria

Location

Novartis Investigative Site

Toronto, Canada

Location

Novartis Investigative Site

Prague, Czechia

Location

Novartis Investigative Site

Bordeaux, France

Location

Novartis Investigative Site

Lyon, France

Location

Novartis Investigative Site

Marseille, France

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Cologne, Germany

Location

Novartis Investigative Site

Düsseldorf, Germany

Location

Novartis Investigative Site

Essen, Germany

Location

Novartis Investigative Site

Frankfurt, Germany

Location

Novartis Investigative Site

Hanover, Germany

Location

Novartis Investigative Site

Mannheim, Germany

Location

Novartis Investigative Site

München, Germany

Location

Novartis Investigative Site

Tübingen, Germany

Location

Novrtis Investigative Site

Bologna, Italy

Location

Novartis Investigative Site

Milan, Italy

Location

Novartis Investigative Site

Leiden, Netherlands

Location

Novartis Investigative Site

Warsaw, Poland

Location

Novartis Investigative Site

Seoul, South Korea

Location

Novartis Investigative Site

Madrid, Spain

Location

Novartis Investigative Site

Chur, Switzerland

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

nilotinib; Imatinib Mesylate; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2007
• First Posted: May 9, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: June 1, 2011
• Last Updated: June 12, 2012
• Results First Posted: May 17, 2011

Record last verified: 2012-06

Locations

CZ (1); AU (2); NL (1); ES (1); DE (9); US (11); CH (1); KR (1); IT (2); FR (3); PL (1); CA (1)