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

This study has been completed.

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00075218

First received: January 6, 2004

Last updated: August 31, 2009

Last verified: August 2009

History of Changes

Results First Received: May 6, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Gastrointestinal Stromal Tumor
Interventions:	Drug: Placebo Drug: 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
Enrollment began (medical clinic) in December 2003. Study was unblinded on 27 January 2005 (end of Double-blind treatment). Subjects experiencing disease progression could crossover to Open-label treatment. Open-label data collection ended May 2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
361 subjects randomized to double-blind treatment in 2:1 ratio (sunitinib vs. Placebo). 255 subjects continued on or crossed over to Open-label treatment.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

361 subjects randomized to double-blind treatment in 2:1 ratio (sunitinib vs. Placebo).

255 subjects continued on or crossed over to Open-label treatment.

Reporting Groups

	Description
Sunitinib Double-Blind Treatment	Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment	Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment	Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Participant Flow for 2 periods

Period 1: Double-Blind Treatment

	Sunitinib Double-Blind Treatment	Placebo Double-Blind Treatment
STARTED	243 ^[1]	118 ^[1]
Received Double-Blind Treatment	228 ^[2]	114 ^[2]
Crossed Over to Open-Label Treatment	152	103
COMPLETED	152 ^[3]	103 ^[3]
NOT COMPLETED	91	15
Adverse Event	23	4
Withdrawal by Subject	7	4
Lost to Follow-up	1	0
Lack of Efficacy	58	6
Decision of Sponsor	0	1
No study medication taken	2	0

[1]	Intent To Treat Population (ITT)
[2]	As Treated Population (AT)
[3]	Defined:subjects completed double-blind treatment phase and/or entered open-label treatment phase.

Period 2: Open-Label Treatment

	Sunitinib Double-Blind Treatment	Placebo Double-Blind Treatment	Sunitinib Open-Label Treatment
STARTED	0	0	255
COMPLETED	0	0	0
NOT COMPLETED	0	0	255
Lack of Efficacy	0	0	174
Adverse Event	0	0	51
Withdrawal by Subject	0	0	12
Decision of Sponsor	0	0	8
Protocol Violation	0	0	1
enrolled in a separate continuation	0	0	9

Baseline Characteristics

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Reporting Groups

	Description
Sunitinib Double-Blind Treatment	Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment	Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Total	Total of all reporting groups

Baseline Measures

	Sunitinib Double-Blind Treatment	Placebo Double-Blind Treatment	Total
Number of Participants [units: participants]	243	118	361
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	170	81	251
>=65 years	73	37	110
Gender [units: participants]
Female	91	71	162
Male	152	47	199

Outcome Measures

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1. Primary:

Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase ]

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2. Primary:

Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV) ]

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3. Secondary:

Progression Free Survival (PFS) [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

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4. Secondary:

Overall Survival Status of Subjects [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

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5. Secondary:

Overall Survival [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

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6. Secondary:

Overall Survival Based on the Rank Preserving Structural Failure Time Method [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

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7. Secondary:

Best Overall Tumor Response During Double-blind Treatment Phase [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

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8. Secondary:

Confirmed Objective Response (CR or PR) in Subjects [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

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9. Secondary:

Time to Tumor Response (TTR) [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

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10. Secondary:

Duration of Performance Status Maintenance [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

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11. Secondary:

Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI) [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

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12. Secondary:

Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI) [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

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Measure Type	Secondary
Measure Title	Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)
Measure Description	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.
Time Frame	Day 1 & 28 of each cycle : duration of double-blind treatment phase
Safety Issue	No

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.
Pain-Relief-Response population.

Reporting Groups

Description

Sunitinib Double-Blind Treatment

Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.

Placebo Double-Blind Treatment

Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.

Measured Values

	Sunitinib Double-Blind Treatment	Placebo Double-Blind Treatment
Number of Participants Analyzed [units: participants]	150	75
Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI) [units: participants]	46	10

Statistical Analysis 1 for Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)

Groups ^[1]	All groups
Method ^[2]	Pearson chi-square
P Value ^[3]	0.0046
Treatment Difference (percent) ^[4]	17.3
95% Confidence Interval	( 6.7 to 28.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	95% CI of Difference based on normal distribution. Percent = (number of subjects with response per total subjects per treatment in defined analysis population)*100.

13. Secondary:

Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS) [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

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14. Secondary:

Change From Baseline in EQ-5D Health State Profile Index [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Limitations and Caveats

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
Duration of Tumor Response could not be reliably estimated at the time of analysis.

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 by Pfizer

Publications automatically indexed to this study:

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.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier:	NCT00075218 History of Changes
Other Study ID Numbers:	A6181004
Study First Received:	January 6, 2004
Results First Received:	May 6, 2009
Last Updated:	August 31, 2009
Health Authority:	United States: Food and Drug Administration

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