Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors

A Phase IIIB, Randomized, Active Controlled Open-Label Study Of Sunitinib (Sutent) 37.5 Mg Daily Vs Imatinib Mesylate 800 Mg Daily In The Treatment Of Patients With Gastrointestinal Stromal Tumors (GIST) Who Have Had Progressive Disease While On 400 Mg Daily Of Imatinib

A phase IIIb study of patients with gastrointestinal stromal tumors who have had progressive disease while on 400 mg imatinib. Patients will be randomly assigned to either sunitinib 37.5 mg daily or imatinib 800 mg daily. This study will find out the benefits and potential side effects of taking sunitinib or imatinib for approximately one year.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: sunitinib malate; Drug: imatinib mesylate

Detailed Description

The study prematurely discontinued on July 27, 2009 due to poor recruitment and operational futility as a result of changes in clinical practice. There were no safety or efficacy concerns regarding the study in the decision to terminate the trial.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Goettingen, Germany, 37075
    • Pfizer Investigational Site
  • Hamburg, Germany, 22767
    • Pfizer Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Pfizer Investigational Site
  • Kowloon
    • Lai Chi Kok, Kowloon, Hong Kong
      • Pfizer Investigational Site
  • New Territories
    • Tuen Mun, New Territories, Hong Kong
      • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Pfizer Investigational Site
  • Milano, Italy, 20133
    • Pfizer Investigational Site
  • San Giovanni Rotondo, Italy, 71013
    • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • Pfizer Investigational Site
  • Valencia, Spain, 46009
    • Pfizer Investigational Site
• United Kingdom
  • Glasgow, United Kingdom, G12 0YH
    • Pfizer Investigational Site
  • Leeds, United Kingdom, LS9 7TF
    • Pfizer Investigational Site
  • London, United Kingdom, SW3 6JJ
    • Pfizer Investigational Site
  • London, United Kingdom, NW1 2PG
    • Pfizer Investigational Site
  • London, United Kingdom, W1
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M20 4BX
    • Pfizer Investigational Site
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Pfizer Investigational Site
    • Farmington Hills, Michigan, United States, 48334
      • Pfizer Investigational Site
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63110
      • Pfizer Investigational Site
    • St. Peters, Missouri, United States, 63376
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • 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

Inclusion Criteria:

• Patients with gastrointestinal stromal tumors whose disease has progressed on imatinib 400 mg daily.

Exclusion Criteria:

• Current treatment with any chemotherapy other than imatinib.
• Current treatment with any dose of imatinib other than 400 mg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B	Drug: imatinib mesylate; 800mg daily
Experimental: A	Drug: sunitinib malate; 37.5 mg daily; Other Names: Sutent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from randomization to the first documentation of tumor progression or death due to any cause in the absence of documented tumor progression, whichever was earlier.	Baseline, Week 5, and every 8 weeks until Year 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from date of randomization to the date of death. In the absence of confirmation of death, survival time was censored to the last date the participant was known to be alive.	Baseline up to 2 years
Time to Pain Relief Response (TTPR)	Pain relief response defined as a 50 percent (%) or more reduction in the McGill Pain Questionaire - Present Pain Intensity (MPQ-PPI) score (0=no pain to 5=excruciating pain) and/or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication.	Day 28 of Cycle 1 up to 26
Time to Treatment Failure (TTF)	TTF included death for any reason, treatment termination due to intolerable toxicity, or withdrawal of consent, whichever occurred first.	Day 28 of Cycle 1 up to 26
Number of Participants With Objective Response of Complete Response or Partial Response	Number of participants with objective response based assessment of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Day 28 of Cycle 1 up to 26
Time to Tumor Response (TTR)	Time from date of randomization to first documentation of objective tumor response (partial or complete response). Confirmed complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Day 28 of Cycle 1 up to 26
Duration of Response (DR)	Time from start of first documentation of objective response(complete or partial response) that was subsequently confirmed to first documentation of objective tumor progression or death due to any cause, whichever occurred first. Confirmed complete response (CR) and partial response (PR)according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions. PR was defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Day 28 of Cycle 1 up to 26
Time to Pain Progression (TTPP)	TTPP is the number of days from randomization to the first documentation of pain progression (defined as a 50% or more increase in MPQ-PPI score [0=no pain to 5=excruciating pain] or analgesic use from baseline for at least 3 consecutive weeks). Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication.	Day 28 of Cycle 1 up to 26
Number of Participants With Pain Relief Response	Pain relief response defined as a 50% or more reduction in the McGill Pain Questionaire - Present Pain Intensity (MPQ-PPI) score (0=no pain to 5=excruciating pain) and/or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication.	Day 28 of Cycle 1 up to 26
Number of Participants With Pain Progression	Pain progression defined as a 50% or more increase in MPQ-PPI score (0=no pain to 5=excruciating pain) or analgesic use from baseline for at least 3 consecutive weeks. Analgesic use scores were based on 1 point per non narcotic dose of medication and 4 points per dose of narcotic medication.	Day 28 of Cycle 1 up to 26
Euro Quality of Life (EQ-5D) - Health State Profile Utility Score- Sunitinib Treatment Arm	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component rated current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicated better health state (no problems); 3 indicated worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigned utility value for each domain in profile. Score was transformed and results in a total score ranged 0.21 to 1.000; higher score indicated a better health state.	Days 1 and 28 of each cycle
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) - Sunitinib Treatment Arm	EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single index value. The VAS component rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicated a better health state.	Days 1 and 28 of each cycle
Euro Quality of Life (EQ-5D) - Health State Profile Utility Score - Imatinib Treatment Arm	EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single utility score. Health State Profile component rated current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicated better health state (no problems); 3 indicated worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigned utility value for each domain in the profile. Score was transformed and results in a total score ranged 0.21 to 1.000; higher score indicated a better health state.	Days 1 and 28 of each cycle
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) - Imatinib Treatment Arm	EQ-5D: participant rated questionnaire assessed health-related quality of life in terms of a single index value. The VAS component rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicated a better health state.	Days 1 and 28 of each cycle

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: September 5, 2006
• First Submitted That Met QC Criteria: September 5, 2006
• First Posted (Estimate): September 7, 2006

Study Record Updates

• Last Update Posted (Estimate): March 17, 2011
• Last Update Submitted That Met QC Criteria: March 15, 2011
• Last Verified: March 1, 2011

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; Imatinib Mesylate
• Other Study ID Numbers: A6181112