A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00457743
First received: April 4, 2007
Last updated: October 2, 2009
Last verified: October 2009
Results First Received: July 16, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Gastrointestinal Stromal Tumors
Intervention: Drug: Sunitinib malate (SU011248)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Phase 1 only included Cycle 1 for subjects enrolled in Phase 1. Phase 2 was comprised of either Cycle 2 and beyond for subjects who were enrolled in Phase 1, or all cycles for newly enrolled subjects. Additional subjects were enrolled to make a total of 30 in the recommended dose level (50-mg).

Reporting Groups
  Description
SU-011248 25-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.

SU-011248 50-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.

From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.

SU-011248 75-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.


Participant Flow:   Overall Study
    SU-011248 25-mg     SU-011248 50-mg     SU-011248 75-mg  
STARTED     3 [1]   30 [1]   3 [1]
Enrolled in Phase 1     3     6     3  
Completed Phase 1     3     6     3  
Enrolled in Phase 2     3 [2]   30 [3]   3 [2]
COMPLETED     0 [4]   3 [5]   0 [6]
NOT COMPLETED     3     27     3  
Adverse Event                 0                 4                 0  
Lack of Efficacy                 3                 23                 3  
[1] Overall study
[2] Three subjects who completed Phase 1 entered Phase 2.
[3] Six subjects who completed Phase 1 entered Phase 2, and 24 subjects were newly enrolled.
[4] However, all 3 subjects enrolled were included in analysis (Intent-to treat population).
[5] However, all 30 subjects enrolled were included in analysis(Intent-to treat population).
[6] However, all 3 subjects enrolled were included in analysis(Intent-to treat population).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
SU-011248 25-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.

SU-011248 50-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.

From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.

SU-011248 75-mg

Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.

Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.

Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.

Total Total of all reporting groups

Baseline Measures
    SU-011248 25-mg     SU-011248 50-mg     SU-011248 75-mg     Total  
Number of Participants  
[units: participants]
  3     30     3     36  
Age, Customized  
[units: participants]
       
18-44 years     2     2     0     4  
45-64 years     1     24     1     26  
>=65 years     0     4     2     6  
Gender  
[units: participants]
       
Female     1     11     0     12  
Male     2     19     3     24  
Region of Enrollment  
[units: participants]
       
Japan     3     30     3     36  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: participants]
       
0     3     18     2     23  
1     0     12     1     13  
[1]

Grade 0: Fully active, able to carry on all pre-disease performance without restriction.

Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.




  Outcome Measures
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1.  Primary:   Number of Subjects With Dose Limiting Toxicities (DLT)   [ Time Frame: Cycle 1 (Baseline to Week 6) ]

2.  Primary:   Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1   [ Time Frame: Day 1 of Cycle 1 ]

3.  Primary:   Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28   [ Time Frame: Day 28 of Cycle 1 ]

4.  Primary:   Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1   [ Time Frame: Day 1 of Cycle 1 ]

5.  Primary:   Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28   [ Time Frame: Day 28 of Cycle 1 ]

6.  Primary:   Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1   [ Time Frame: Day 1 of Cycle 1 ]

7.  Primary:   Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28   [ Time Frame: Day 28 of Cycle 1 ]

8.  Primary:   SU-011248 Clearance on Cycle 1 Day 28   [ Time Frame: Day 28 of Cycle 1 ]

9.  Primary:   Accumulation Ratio (Rac) on Cycle 1 Day 28   [ Time Frame: Day 28 of Cycle 1 ]

10.  Primary:   Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group   [ Time Frame: Day 28 of Cycles 1-4 ]

11.  Secondary:   Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)   [ Time Frame: Day 1, 14, 28 of Cycles 1-4 ]

12.  Secondary:   Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)   [ Time Frame: Day 1, 14, 28 of Cycles 1-4 ]

13.  Secondary:   Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)   [ Time Frame: Day 1, 14, 28 of Cycles 1-4 ]

14.  Secondary:   Trough Plasma Concentration (Ctrough) of SU-011248   [ Time Frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 ]

15.  Secondary:   Trough Plasma Concentration (Ctrough) of SU-012262   [ Time Frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 ]

16.  Secondary:   Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662   [ Time Frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 ]

17.  Secondary:   Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires   [ Time Frame: Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4 ]

18.  Secondary:   Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires   [ Time Frame: Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4 ]

19.  Secondary:   Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group   [ Time Frame: Day 28 of Cycles 1-4 ]

20.  Secondary:   Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group   [ Time Frame: Day 28 of Cycles 1-4 ]

21.  Secondary:   Time To Tumor Progression (TTP)   [ Time Frame: From the first dose to Progressive Disease ]

22.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: From the first dose to Progressive Disease or Death ]

23.  Secondary:   Time To Failure (TTF)   [ Time Frame: From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer. ]

24.  Secondary:   Overall Survival Time   [ Time Frame: From the first dose to death ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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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  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided


Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00457743     History of Changes
Other Study ID Numbers: A6181045, JapicCTI-070386
Study First Received: April 4, 2007
Results First Received: July 16, 2009
Last Updated: October 2, 2009
Health Authority: Japan: Ministry of Health, Labor and Welfare