A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Of SU011248 In The Treatment Of Patients With Imatinib Mesylate (Gleevec Tm, Glivec)-Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor

A study to assess the safety and efficacy of SU11248 in patients with gastrointestinal stromal tumor (GIST) whose disease has failed imatinib therapy or who were intolerant to imatinib treatment.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Placebo; Drug: SU011248

• Study Type: Interventional
• Enrollment (Actual): 361
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Pfizer Investigational Site
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Pfizer Investigational Site
    • Randwick, New South Wales, Australia, 2031
      • Pfizer Investigational Site
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Pfizer Investigational Site
  • South Australia
    • Ashford, South Australia, Australia, 5035
      • Pfizer Investigational Site
    • Bedford Park, South Australia, Australia, 5042
      • Pfizer Investigational Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Pfizer Investigational Site
• Belgium
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Pfizer Investigational Site
• France
  • Lyon, France, 69373
    • Pfizer Investigational Site
  • Marseille, France, 13385
    • Pfizer Investigational Site
  • VILLEJUIF Cedex, France, 94805
    • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Pfizer Investigational Site
  • Genova, Italy, 16132
    • Pfizer Investigational Site
  • Milano, Italy, 20162
    • Pfizer Investigational Site
  • Milano, Italy, 20133
    • Pfizer Investigational Site
  • Milano, Italy, 20141
    • Pfizer Investigational Site
  • Torino, Italy, 10153
    • Pfizer Investigational Site
  • PN
    • Aviano, PN, Italy, 33081
      • Pfizer Investigational Site
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Pfizer Investigational Site
• Netherlands
  • Gr
    • Groningen, Gr, Netherlands, 9713 GZ
      • Pfizer Investigational Site
  • ZH
    • Rotterdam, ZH, Netherlands, 3075 EA
      • Pfizer Investigational Site
• Singapore
  • Singapore, Singapore, 119074
    • Pfizer Investigational Site
  • Singapore, Singapore, 169610
    • Pfizer Investigational Site
  • Singapore, Singapore, 308433
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08025
    • Pfizer Investigational Site
  • Madrid, Spain, 28041
    • Pfizer Investigational Site
  • Barcelona
    • L'Hospitalet del Llobregat, Barcelona, Spain, 08907
      • Pfizer Investigational Site
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Pfizer Investigational Site
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Pfizer Investigational Site
  • London, United Kingdom, W1T 3AA
    • Pfizer Investigational Site
  • Newcastle-Upon-Tyne, United Kingdom, NE4 6BE
    • Pfizer Investigational Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5NG
      • Pfizer Investigational Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095-6984
      • Pfizer Investigational Site
    • Pasadena, California, United States, 91105
      • Pfizer Investigational Site
    • Santa Monica, California, United States, 90404
      • Pfizer Investigational Site
    • Stanford, California, United States, 94305
      • Pfizer Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Pfizer Investigational Site
  • Florida
    • Miami, Florida, United States, 33136
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33612
      • Pfizer Investigational Site
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Pfizer Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Pfizer Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Pfizer Investigational Site
    • New York, New York, United States, 10021-6007
      • Pfizer Investigational Site
    • New York, New York, United States, 10022
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195-0002
      • Pfizer Investigational Site
    • Columbus, Ohio, United States, 43210
      • Pfizer Investigational Site
    • Columubs, Ohio, United States, 43210
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97201
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Pfizer Investigational Site
    • Seattle, Washington, United States, 98109
      • Pfizer Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Histologically-proven diagnosis of malignant GIST not amenable to surgery, radiation or combined modality treatment with curative intent
• Failed Gleevec treatment or intolerant to Gleevec therapy

Key Exclusion Criteria:

• Treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational agent since the last dose of Gleevec

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A	Drug: SU011248; 50 mg taken orally once a day. 6 week treatment cycle (Schedule 4/2) 4 weeks on study drug/2 weeks off study drug.
PLACEBO_COMPARATOR: B	Drug: Placebo; 50 mg taken orally once a day. 6 week treatment cycle (Schedule 4/2) 4 weeks on study drug/2 weeks off study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase	Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors).	Day 28 of each 6-week cycle : duration of double-blind treatment phase
Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study	Time from randomization to first documentation of objective tumor progression based on the assessment of an independent, third-party imaging laboratory using RECIST (Response Evaluation Criteria in Solid Tumors).	Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from randomization to first documentation of objective tumor progression or to death due to any cause (on treatment or within 28 days of last dose).	Day 28 of each cycle : duration of double-blind treatment phase
Overall Survival Status of Subjects	Number of subjects alive at end of study.	clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug
Overall Survival	Time from date of randomization to date of death due to any cause.	clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug
Overall Survival Based on the Rank Preserving Structural Failure Time Method	time from date of randomization to date of death due to any cause (rank preserving structural failure time method).	clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug
Best Overall Tumor Response During Double-blind Treatment Phase	Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST).	Day 28 of each cycle : duration of double-blind treatment phase
Confirmed Objective Response (CR or PR) in Subjects	Overall confirmed objective response = confirmed Complete Response (CR) OR confirmed Partial Response (PR) according to RECIST. Confirmed responses were those that persisted on repeat imaging study ≥ 4 weeks after initial documentation of response.	Day 28 of each cycle : duration of double-blind treatment phase
Time to Tumor Response (TTR)	Time from date of randomization to first documentation of objective tumor response that was subsequently confirmed. TTR was only calculated for the subgroup of subjects with a confirmed objective tumor response.	Day 28 of each cycle : duration of double-blind treatment phase
Duration of Performance Status Maintenance	Time from randomization until the last time the performance status was no worse than at baseline or to death due to cancer in the absence of previous documentation of performance status worsening.	Day 28 of each cycle : duration of double-blind treatment phase
Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)	25th Quartile: Time to Progression. Progression: a) No change (NC) in MPQ-PPI score (0=no pain to 5=excruciating pain) with increase total analgesic use >= 50% over baseline OR b) Increase score >= 1 point with either NC in total analgesic use or increase total analgesic use >= 50% over baseline. (50th Quartile not achieved.)	Day 1 & 28 of each cycle : duration of double-blind treatment phase
Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)	MPQ-PPI: 0=no pain to 5= excruciating pain. Pain Relief Response= 1) Decrease by >= 1 points in MPQ-PPI score with either Decrease or No Change in total analgesic use >= 50% over baseline OR 2) No change in MPQ-PPI score with Decrease total analgesic use >= 50% over baseline.	Day 1 & 28 of each cycle : duration of double-blind treatment phase
Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)	Change: median score at observation minus median score at baseline. EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state.	Day 1 & 28 of each cycle : duration of double-blind treatment phase
Change From Baseline in EQ-5D Health State Profile Index	Change: median index score at observation minus median index score at baseline. EQ-5D is a generic instrument that describes health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) with a weighted health Index based on general population values where where 0.0 = death and 1.0 = perfect health.	Day 1 & 28 of each cycle : duration of double-blind treatment phase

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. doi: 10.1016/S0140-6736(06)69446-4.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): May 1, 2008
• Study Completion (ACTUAL): May 1, 2008

Study Registration Dates

• First Submitted: January 6, 2004
• First Submitted That Met QC Criteria: January 7, 2004
• First Posted (ESTIMATE): January 8, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): September 28, 2009
• Last Update Submitted That Met QC Criteria: August 31, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: A6181004