A Safety Study Of Sunitinib In Combination With Pemetrexed In Patients With Advanced Solid Malignancies - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Neoplasm, Malignant
Intervention:	Drug: Sunitinib, Pemetrexed

Participant Flow

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
No text entered.

Reporting Groups

	Description
Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.
Sunitinib 50 mg/Day Schedule-2/1	Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Description

Sunitinib 37.5 mg/Day Continuous Daily Dosing

Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Sunitinib 50 mg/Day Schedule-2/1

Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment.

Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Participant Flow: Overall Study

	Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 50 mg/Day Schedule-2/1
STARTED	6	6
COMPLETED	0	0
NOT COMPLETED	6	6
Adverse Event	1	1
Objective Progression or Relapse	3	5
Global Deterioration of Health Status	1	0
Withdrawal by Subject	1	0

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.
Sunitinib 50 mg/Day Schedule-2/1	Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.
Total	Total of all reporting groups

Description

Sunitinib 37.5 mg/Day Continuous Daily Dosing

Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Sunitinib 50 mg/Day Schedule-2/1

Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment.

Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Total

Total of all reporting groups

Baseline Measures

	Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 50 mg/Day Schedule-2/1	Total
Number of Participants [units: participants]	6	6	12
Age, Customized [units: Participants]
20-44 years	0	0	0
45- 64 years	4	2	6
>=65 years	2	4	6
Gender [units: Participants]
Female	0	2	2
Male	6	4	10
Eastern Cooperative Oncology Group (ECOG) Performance Status ^[1] [units: Participants]
Score 0	2	4	6
Score 1	4	2	6

[1]	Score 0: Fully active, able to carry on all pre-disease performance without restriction; Score 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light house work and office work.

Outcome Measures

Show All Outcome Measures

1. Primary:

Number of Participants With Adverse Events [ Time Frame: End of study (up to individual discontinuation) ]

Show Outcome Measure 1

2. Secondary:

Sunitinib Relative Dose Intensity in the "Sunitinib 37.5 mg/Day Continuous Daily Dosing" Treatment Arm [ Time Frame: Up to Cycle 5 (end of study) ]

Show Outcome Measure 2

3. Secondary:

Sunitinib Relative Dose Intensity in the "Sunitinib 50 mg/Day Schedule-2/1" Treatment Arm [ Time Frame: Up to Cycle 6 ]

Show Outcome Measure 3

4. Secondary:

Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 4

5. Secondary:

AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 5

6. Secondary:

Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 6

7. Secondary:

Maximum Concentration of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 7

8. Secondary:

AUC0-∞ of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 8

9. Secondary:

Terminal Phase Elimination Half-Life (T1/2) of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose ]

Show Outcome Measure 9

10. Secondary:

Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15 [ Time Frame: Cycle 1 Day 14 (or 15): approximately 24 hours after the previous dose ]

Show Outcome Measure 10

11. Secondary:

Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants [ Time Frame: End of study (Up to individual study discontinuation) ]

Show Outcome Measure 11

Serious Adverse Events

Hide Serious Adverse Events

Time Frame	No text entered.
Additional Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Reporting Groups

	Description
Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.
Sunitinib 50 mg/Day Schedule-2/1	Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Description

Sunitinib 37.5 mg/Day Continuous Daily Dosing

Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Sunitinib 50 mg/Day Schedule-2/1

Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment.

Pemetrexed 500 mg/m^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle.

Serious Adverse Events

	Sunitinib 37.5 mg/Day Continuous Daily Dosing	Sunitinib 50 mg/Day Schedule-2/1
Total, serious adverse events
# participants affected / at risk	2/6 (33.33%)	1/6 (16.67%)
Blood and lymphatic system disorders
Febrile neutropenia ^{† 1}
# participants affected / at risk	0/6 (0.00%)	1/6 (16.67%)
General disorders
Pyrexia ^{† 1}
# participants affected / at risk	0/6 (0.00%)	1/6 (16.67%)
Infections and infestations
Enterocolitis infectious ^{† 1}
# participants affected / at risk	1/6 (16.67%)	0/6 (0.00%)
Metabolism and nutrition disorders
Dehydration ^{† 1}
# participants affected / at risk	2/6 (33.33%)	0/6 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion ^{† 1}
# participants affected / at risk	0/6 (0.00%)	1/6 (16.67%)
Pneumothorax ^{† 1}
# participants affected / at risk	0/6 (0.00%)	1/6 (16.67%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 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.gov_Inquiries@pfizer.com

No publications provided by Pfizer

Publications automatically indexed to this study:

Okamoto I, Shimizu T, Miyazaki M, Tsurutani J, Ichikawa Y, Terashima M, Takeda M, Fumita S, Ohki E, Kimura N, Hashimoto J, Nakagawa K. Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors. Invest New Drugs. 2012 Apr;30(2):639-46. Epub 2010 Oct 20.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00732992 History of Changes
Other Study ID Numbers:	A6181165
Study First Received:	August 8, 2008
Results First Received:	October 27, 2010
Last Updated:	March 15, 2011
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency