Study Of SU011248 Plus Gefitinib (Iressa) In Patients With Advanced Renal Cell Carcinoma

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT00113529

First received: June 8, 2005

Last updated: August 25, 2011

Last verified: August 2011

History of Changes

Results First Received: March 1, 2010

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:	Carcinoma, Renal Cell
Intervention:	Drug: Gefitinib + Sunitinib

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 11 subjects enrolled in Phase 1. Phase 2 included 4 subjects from Phase 1 (37.5 mg sunitinib Cohort) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib Cohort), for a total of 35 subjects.

Reporting Groups

	Description
Sunitinib + Gefitinib	Phase 2 included 4 subjects from Phase 1 (37.5 milligrams (mg) or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.

Description

Sunitinib + Gefitinib

Phase 2 included 4 subjects from Phase 1 (37.5 milligrams (mg) or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.

Participant Flow: Overall Study

	Sunitinib + Gefitinib
STARTED	35 ^[1]
COMPLETED	1 ^[2]
NOT COMPLETED	34
Adverse Event	4
Lack of Efficacy	20
Decision of sponsor	6
Withdrawal by Subject	4

[1]	Phase 2 included 4 subjects from Phase 1 and 31 from Phase 2, for a total of 35 subjects.
[2]	Subject discontinued from the study and continued treatment on commercially available sunitinib.

Baseline Characteristics

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Reporting Groups

	Description
Sunitinib + Gefitinib	Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.

Description

Sunitinib + Gefitinib

Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.

Baseline Measures

	Sunitinib + Gefitinib
Number of Participants [units: participants]	35
Age, Customized [units: participants]
< 65 years	19
> = 65 years	16
Gender [units: participants]
Female	9
Male	26

Outcome Measures

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1. Primary:

Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter ]

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2. Secondary:

Time to Tumor Response (TTR) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter ]

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3. Secondary:

Duration of Response (DR) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancer ]

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4. Secondary:

Time to Tumor Progression (TTP) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter ]

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5. Secondary:

Overall Survival (OS) [ Time Frame: From start of study treatment until death ]

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6. Secondary:

Progression-Free Survival (PFS) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death ]

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7. Secondary:

Probability of Survival at One Year [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year ]

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8. Secondary:

VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ]

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9. Secondary:

VEGF Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ]

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10. Secondary:

VEGF-C Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ]

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11. Secondary:

VEGF-C Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ]

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12. Secondary:

Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ]

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13. Secondary:

sVEGFR2 Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ]

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14. Secondary:

Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ]

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15. Secondary:

sVEGFR3 Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ]

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16. Secondary:

Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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17. Secondary:

Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

Show Outcome Measure 17

18. Secondary:

Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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20. Secondary:

Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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21. Secondary:

Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

Show Outcome Measure 21

22. Secondary:

Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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Measure Type	Secondary
Measure Title	Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Measure Description	Change = median VEGFR2 level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
Time Frame	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive
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.
ITT. Number of participants analyzed = number of subjects evaluable for PFS (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.

Reporting Groups

	Description
Sunitinib + Gefitinib	Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.

Description

Sunitinib + Gefitinib

Measured Values

	Sunitinib + Gefitinib
Number of Participants Analyzed [units: participants]	16
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median [units: pg/mL]
Cycle 1, Day 1 (PFS >= Median, n=5)	9100.00
Cycle 1, Day 1 (PFS < Median, n=11)	10145.00
Cycle 1, Day 28 (PFS >= Median, n=5)	0.56
Cycle 1, Day 28 (PFS < Median, n=10)	0.69
Cycle 2, Day 1 (PFS >= Median, n=5)	0.79
Cycle 2, Day 1 (PFS < Median, n=9)	0.78
Cycle 2, Day 28 (PFS >= Median, n=5)	0.56
Cycle 2, Day 28 (PFS < Median, n=8)	0.64
Cycle 3, Day 1 (PFS >= Median, n=5)	0.74
Cycle 3, Day 1 (PFS < Median, n=8)	0.75
Cycle 3, Day 28 (PFS >= Median, n=5)	0.52
Cycle 3, Day 28 (PFS < Median, n=6)	0.62

Statistical Analysis 1 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	0.910

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 1, Day 1
[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.

Statistical Analysis 2 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	0.020

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 1, Day 28
[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.

Statistical Analysis 3 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	1.000

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 2, Day 1
[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.

Statistical Analysis 4 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	0.509

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 2, Day 28
[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.

Statistical Analysis 5 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	0.883

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 3, Day 1
[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.

Statistical Analysis 6 for Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median

Groups ^[1]	Sunitinib + Gefitinib
Method ^[2]	Wilcoxon Rank Sum Test
P Value ^[3]	0.582

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 3, Day 28
[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.

23. Secondary:

Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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24. Secondary:

Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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25. Secondary:

Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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26. Secondary:

Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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27. Secondary:

Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ]

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28. Secondary:

Trough Plasma Concentrations (Ctrough) of Sunitinib [ Time Frame: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) ]

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29. Secondary:

Ctrough of SU-012662 (Sunitinib's Metabolite) [ Time Frame: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) ]

Show Outcome Measure 29

30. Secondary:

Ctrough of Gefitinib [ Time Frame: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) ]

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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
No text entered.

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:

Motzer RJ, Hudes GR, Ginsberg MS, Baum MS, Harmon CS, Kim ST, Chen I, Redman BG. Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal cell carcinoma. Am J Clin Oncol. 2010 Dec;33(6):614-8.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00113529 History of Changes
Other Study ID Numbers:	A6181038
Study First Received:	June 8, 2005
Results First Received:	March 1, 2010
Last Updated:	August 25, 2011
Health Authority:	United States: Food and Drug Administration

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