Open Label Study Of SU011248 In Combination With Trastuzumab For Patients With Metastatic Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00243503
• Collaborator: (none)
• Enrollment: 60
• Locations: 27
• Arm: 1
• Duration (Months): 52.9
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The current study is to evaluate: Overall response rate for the combination of trastuzumab and SU011248 in metastatic or locally recurrent breast cancer; evaluate safety and tolerability of the combination; measure duration of tumor control and survival; assess patient reported outcomes; assess PK in combination with trastuzumab and compare efficacy and safety.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: SU011248/Trastuzumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Efficacy And Safety Study Of SU011248 In Combination With Trastuzumab As Treatment For Metastatic Disease In Patients With Breast Cancer
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: A

Drug: SU011248/Trastuzumab; SU011248 will be administered orally, starting dose of 37.5 mg daily on a continuous regimen. Trastuzumab will be administered weekly (loading dose 4 mg/kg followed by weekly 2mg/kg) or every 3 weeks (loading dose 8 mg/kg followed by 6mg/kg q3w). Study treatment should continue until progression, withdrawal for other reasons, or for up to 18 months following which patients requiring continued access will be offered SU011248 on a separate protocol.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Overall Confirmed Objective Disease Response [From start of treatment through 18 months]

   Objective disease response =participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target and non-target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions associated to a non-progressive disease response for the non target lesions.

Secondary Outcome Measures

1. Duration of Response (DR) [From start of treatment through 18 months]

   Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1) divided by 7.

2. Percentage of Participants With Clinical Benefit [From start of treatment through 18 months]

   Percent of participants with confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST.CR was defined as disappearance of all target and non-target lesions.PR was defined as >=30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions associated to non-progressive disease response for non target lesions.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started.

3. Progression Free Survival (PFS) [From start of treatment through 18 months]

   Time from first dose of study treatment to first documentation of objective tumor progression, or to death on-study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS was calculated as (first event date minus first dose date +1) divided by 7.

4. Time to Progression (TTP) [From start of treatment through 18 months]

   Time from first dose of study treatment to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP was calculated as (first event date minus first dose date +1) divided by 7.

5. Overall Survival (OS) [From start of study treatment until death or 2 years from first study treatment]

   Time from first dose of study treatment to first documentation of death due to any cause. OS was calculated as (date of death minus first dose date +1) divided by 7 * 4.33.

6. Probability of Survival at One Year [From start of study treatment until death or 2 years from first study treatment]

   One- year survival probability was estimated using the Kaplan-Meier method.

7. EORTC QLQ-C30 [From start of treatment through 18 months]

   EORTC QLQ-C30 scales consist of 30 questions: functional (physical/role/cognitive/emotional/ social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms.

8. EORTC QLQ (BR23) [From start of treatment through 18 months]

   BR23: consisted of 23 questions which measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

9. Dose-corrected Trough Plasma Concentrations (Ctrough) of Sunitinib [Predose on Day 1 of Cycle 3 and 5]

   Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.

10. Dose-corrected Ctrough of SU-012662 (Sunitinib's Metabolite) [Predose on Day 1 of Cycle 3 and 5]

    Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.

11. Dose-corrected Ctrough of Total Drug (Sunitinib + SU-012662) [Predose on Day 1 of Cycle 3 and 5]

    Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A diagnosis of breast cancer with evidence of 1) unresectable, locally recurrent, or

1. metastatic disease.

• HER2 positive disease (3+ by immunohistochemistry [IHC] or FISH-positive)

• Candidate for treatment with trastuzumab. Prior treatment with trastuzumab and or/ lapatinib in the neoadjuvant, adjuvant or metastatic disease setting is permitted. Treatment with hormone therapy in the adjuvant and/or advanced disease setting is permitted.

Exclusion Criteria:

• Prior treatment with >1 regimen of cytotoxic therapy in the advanced disease setting. Adjuvant chemotherapy is permitted

• Prior exposure to trastuzumab if the patient had developed severe hypersensitivity reactions.

• Prior treatment on a SU11248 clinical trial.

• Uncontrolled brain metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Montgomery	Alabama	United States	36106
2	Pfizer Investigational Site	Newark	Delaware	United States	19713
3	Pfizer Investigational Site	Newark	Delaware	United States	19718-6001
4	Pfizer Investigational Site	Wilmington	Delaware	United States	19899
5	Pfizer Investigational Site	Fort Lauderdale	Florida	United States	33308
6	Pfizer Investigational Site	Harvey	Illinois	United States	60426
7	Pfizer Investigational Site	Tinley Park	Illinois	United States	60477
8	Pfizer Investigational Site	Munster	Indiana	United States	46321
9	Pfizer Investigational Site	Lafayette	Louisiana	United States	70503
10	Pfizer Investigational Site	New Iberia	Louisiana	United States	70563
11	Pfizer Investigational Site	Corinth	Mississippi	United States	38834
12	Pfizer Investigational Site	Southaven	Mississippi	United States	38671
13	Pfizer Investigational Site	Las Vegas	Nevada	United States	89135
14	Pfizer Investigational Site	New York	New York	United States	10021
15	Pfizer Investigational Site	Memphis	Tennessee	United States	38104
16	Pfizer Investigational Site	Memphis	Tennessee	United States	38120
17	Pfizer Investigational Site	Ottignies		Belgium	1340
18	Pfizer Investigational Site	Wilrijk		Belgium	2610
19	Pfizer Investigational Site	Toronto	Ontario	Canada	M4N 3M5
20	Pfizer Investigational Site	Greenfield Park	Quebec	Canada	J4V 2H1
21	Pfizer Investigational Site	Montreal	Quebec	Canada	H3G 1A4
22	Pfizer Investigational Site	Besancon		France	25030
23	Pfizer Investigational Site	Lyon		France	69373
24	Pfizer Investigational Site	Saint Cloud		France	92210
25	Pfizer Investigational Site	Barcelona		Spain	08003
26	Pfizer Investigational Site	Madrid		Spain	28040
27	Pfizer Investigational Site	Valencia		Spain	46010

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00243503
• Other Study ID Numbers: A6181067
• First Posted: Oct 24, 2005
• Last Update Posted: Jul 22, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: Breast Cancer Metastatic
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Period Title: Overall Study
STARTED	60
COMPLETED	2
NOT COMPLETED	58

Baseline Characteristics

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Overall Participants	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.1 (12.8)
Sex: Female, Male (Count of Participants)
Female	60 100%
Male	0 0%
EORTC QLQ-C30 (scores on a scale) [Mean (Standard Deviation) ]
Function Score: Global health (n=48)	66.8 (26.8)
Function Score: Physical function (n=49)	79.5 (21.3)
Function Score: Role function (n=49)	76.2 (30.0)
Function Score: Cognitive function (n=49)	82.0 (25.6)
Function Score: Emotional function (n=49)	62.8 (26.4)
Function Score: Social function (n=49)	75.5 (29.9)
Symptom Score: Fatigue (n=49)	35.6 (27.6)
Symptom Score: Pain (n=49)	38.8 (33.7)
Symptom Score: Nausea/vomiting (n=49)	7.1 (18.0)
Symptom Score: Dyspnea (n=48)	22.9 (28.5)
Symptom Score: Loss of appetite (n=49)	14.3 (28.1)
Symptom Score: Insomnia (n=49)	35.4 (31.5)
Symptom Score: Constipation (n=48)	18.1 (32.9)
Symptom Score: Diarrhea (n=49)	6.8 (15.2)
Symptom Score: Financial difficulty (n=48)	15.3 (28.3)
EORTC QLQ Breast Cancer Module (BR23) (scores on a scale) [Mean (Standard Deviation) ]
Function Score : Body image (n=46)	77.2 (25.4)
Function Score: Sexual function (n=44)	21.6 (24.5)
Function Score: Sexual enjoyment (n=15)	53.3 (21.1)
Symptom Score: Arm (n=48)	23.8 (25.3)
Symptom Score: Breast (n=47)	25.9 (27.5)
Symptom Score: systemic therapy side effects(n=48)	17.2 (17.4)
Others :Upset of hair loss (n=6)	50.0 (27.9)
Others :Future health perspective (n=48)	39.6 (32.0)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Overall Confirmed Objective Disease Response
Description	Objective disease response =participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target and non-target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions associated to a non-progressive disease response for the non target lesions.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Number (95% Confidence Interval) [percentage of participants]	36.8 61.3%

2. Secondary Outcome

Title	Duration of Response (DR)
Description	Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or death due to any cause. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1) divided by 7.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

DR was calculated for the subgroup of participants from the ITT set, with a confirmed objective tumor response.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles
Measure Participants	21
Median (95% Confidence Interval) [weeks]	25.6

3. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit
Description	Percent of participants with confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST.CR was defined as disappearance of all target and non-target lesions.PR was defined as >=30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions associated to non-progressive disease response for non target lesions.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Number (95% Confidence Interval) [Percentage of Participants]	56.1 93.5%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Time from first dose of study treatment to first documentation of objective tumor progression, or to death on-study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS was calculated as (first event date minus first dose date +1) divided by 7.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Median (95% Confidence Interval) [Weeks]	28.0

5. Secondary Outcome

Title	Time to Progression (TTP)
Description	Time from first dose of study treatment to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP was calculated as (first event date minus first dose date +1) divided by 7.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Median (95% Confidence Interval) [weeks]	26.0

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Time from first dose of study treatment to first documentation of death due to any cause. OS was calculated as (date of death minus first dose date +1) divided by 7 * 4.33.
Time Frame	From start of study treatment until death or 2 years from first study treatment

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Median (95% Confidence Interval) [months]	NA

7. Secondary Outcome

Title	Probability of Survival at One Year
Description	One- year survival probability was estimated using the Kaplan-Meier method.
Time Frame	From start of study treatment until death or 2 years from first study treatment

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Number (95% Confidence Interval) [percentage of 1-year survival]	91.2

8. Secondary Outcome

Title	EORTC QLQ-C30
Description	EORTC QLQ-C30 scales consist of 30 questions: functional (physical/role/cognitive/emotional/ social), symptom (fatigue/nausea/vomiting/pain), global health/QOL, cancer symptom (dyspnea/insomnia/appetite loss/constipation/diarrhea). Feelings in past week: response range: not at all to very much, global/QOL range: very poor to excellent. Scales/single-items averaged, score 0 to 100. Higher functional/global=better functioning and symptom=greater degree of symptoms.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Function Score: Global health (n=28)	56.0 (21.4)
Function Score: Physical function (n=28)	75.2 (16.8)
Function Score: Role function (n=28)	60.1 (28.8)
Function Score: Cognitive function (n=28)	84.5 (21.7)
Function Score: Emotional function (n=28)	66.1 (27.5)
Function Score: Social function (n=28)	66.7 (28.3)
Symptom Score: Fatigue (n=28)	45.0 (25.3)
Symptom Score: Pain (n=28)	36.9 (25.8)
Symptom Score: Nausea/vomiting (n=28)	6.5 (10.5)
Symptom Score: Dyspnea (n=28)	26.2 (30.6)
Symptom Score: Loss of appetite (n=28)	20.2 (24.6)
Symptom Score: Insomnia (n=28)	29.8 (27.7)
Symptom Score: Constipation (n=27)	14.8 (26.7)
Symptom Score: Diarrhea (n=27)	32.1 (32.7)
Symptom Score: Financial difficulty (n=28)	17.9 (29.4)

9. Secondary Outcome

Title	EORTC QLQ (BR23)
Description	BR23: consisted of 23 questions which measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time Frame	From start of treatment through 18 months

Outcome Measure Data

Analysis Population Description

The ITT population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	57
Function Score : Body image (n=27)	76.4 (29.5)
Function Score: Sexual function (n=24)	14.6 (16.5)
Function Score: Sexual enjoyment (n=10)	33.3 (15.7)
Others :Future health perspective (n=27)	45.7 (34.8)
Symptom Score: systemic therapy side effects(n=27)	21.7 (15.8)
Symptom Score: Breast (n=27)	19.4 (23.6)
Symptom Score: Arm (n=27)	21.0 (23.9)
Others :Upset of hair loss (n=6)	44.4 (27.2)

10. Secondary Outcome

Title	Dose-corrected Trough Plasma Concentrations (Ctrough) of Sunitinib
Description	Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.
Time Frame	Predose on Day 1 of Cycle 3 and 5

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib) and collected plasma values.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	47
Day 1 (Cycle 3)	53.5 (27.6)
Day 1 (Cycle 5)	55.0 (24.8)

11. Secondary Outcome

Title	Dose-corrected Ctrough of SU-012662 (Sunitinib's Metabolite)
Description	Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.
Time Frame	Predose on Day 1 of Cycle 3 and 5

Outcome Measure Data

Analysis Population Description

The PK population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib) and collected plasma values.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	47
Day 1 (Cycle 3)	26.7 (14.4)
Day 1 (Cycle 5)	24.7 (12.5)

12. Secondary Outcome

Title	Dose-corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Description	Ctrough = the concentration prior to study drug administration. Dose-corrected values were reported, the reference dose was 37.5 mg.
Time Frame	Predose on Day 1 of Cycle 3 and 5

Outcome Measure Data

Analysis Population Description

The PK population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib) and collected plasma values.

Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
Measure Participants	47
Day 1 (Cycle 3)	80.2 (39.9)
Day 1 (Cycle 5)	79.7 (36.3)

Adverse Events

Time Frame	From time of informed consent signing (SAEs) or first study treatment (AEs) through 18 months and including 28 calendar days after the last dose of study drug.
Adverse Event Reporting 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.
Arm/Group Title	Trastuzumab + Sunitinib
Arm/Group Description	Trastuzumab was administered intravenously (i.v) weekly (loading 4 mg/kg followed by weekly 2 mg/kg) or every 3 weeks (loading 8 mg/kg followed by 6 mg/kg thrice weekly). Sunitinib began with 37.5 mg by oral capsule once daily in a continuous regimen. Treatment was administered in 4-week cycles.
All Cause Mortality
	Trastuzumab + Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trastuzumab + Sunitinib
	Affected / at Risk (%)	# Events
Total	25/60 (41.7%)
Blood and lymphatic system disorders
Anaemia	1/60 (1.7%)
Febrile neutropenia	2/60 (3.3%)
Idiopathic thrombocytopenic purpura	1/60 (1.7%)
Thrombocytopenia	3/60 (5%)
Cardiac disorders
Cardiac failure	1/60 (1.7%)
Cardiac failure acute	1/60 (1.7%)
Cardiogenic shock	1/60 (1.7%)
Left ventricular dysfunction	1/60 (1.7%)
Gastrointestinal disorders
Anal fistula	1/60 (1.7%)
Oesophageal haemorrhage	1/60 (1.7%)
Oesophagitis	1/60 (1.7%)
Pancreatitis	2/60 (3.3%)
Periodontal disease	1/60 (1.7%)
Vomiting	2/60 (3.3%)
General disorders
Asthenia	2/60 (3.3%)
Multi-organ failure	1/60 (1.7%)
Drug interaction	1/60 (1.7%)
Hepatobiliary disorders
Cholecystitis	1/60 (1.7%)
Infections and infestations
Cellulitis	1/60 (1.7%)
Pilonidal cyst	1/60 (1.7%)
Sepsis	1/60 (1.7%)
Skin infection	1/60 (1.7%)
Device related infection	1/60 (1.7%)
Investigations
Ejection fraction decreased	1/60 (1.7%)
Metabolism and nutrition disorders
Hypercalcaemia	1/60 (1.7%)
Hyponatraemia	1/60 (1.7%)
Decreased appetite	1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Bone pain	1/60 (1.7%)
Nervous system disorders
Headache	1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/60 (1.7%)
Epistaxis	2/60 (3.3%)
Pulmonary embolism	1/60 (1.7%)
Vascular disorders
Hypertension	2/60 (3.3%)
Other (Not Including Serious) Adverse Events
	Trastuzumab + Sunitinib
	Affected / at Risk (%)	# Events
Total	59/60 (98.3%)
Blood and lymphatic system disorders
Anaemia	8/60 (13.3%)
Leukopenia	6/60 (10%)
Neutropenia	17/60 (28.3%)
Thrombocytopenia	16/60 (26.7%)
Cardiac disorders
Left ventricular dysfunction	10/60 (16.7%)
Ear and labyrinth disorders
Vertigo	3/60 (5%)
Endocrine disorders
Hypothyroidism	5/60 (8.3%)
Eye disorders
Eyelid oedema	6/60 (10%)
Lacrimation increased	6/60 (10%)
Gastrointestinal disorders
Abdominal pain	11/60 (18.3%)
Abdominal pain upper	8/60 (13.3%)
Constipation	10/60 (16.7%)
Diarrhoea	36/60 (60%)
Dry mouth	3/60 (5%)
Dyspepsia	20/60 (33.3%)
Gingival bleeding	4/60 (6.7%)
Gingival pain	3/60 (5%)
Nausea	20/60 (33.3%)
Rectal haemorrhage	3/60 (5%)
Stomatitis	8/60 (13.3%)
Vomiting	21/60 (35%)
Abdominal distension	3/60 (5%)
Cheilitis	3/60 (5%)
Haemorrhoids	3/60 (5%)
General disorders
Asthenia	29/60 (48.3%)
Chest pain	3/60 (5%)
Chills	5/60 (8.3%)
Fatigue	19/60 (31.7%)
Mucosal inflammation	21/60 (35%)
Oedema peripheral	4/60 (6.7%)
Pain	4/60 (6.7%)
Pyrexia	11/60 (18.3%)
Infections and infestations
Nasopharyngitis	5/60 (8.3%)
Urinary tract infection	3/60 (5%)
Investigations
Ejection fraction decreased	13/60 (21.7%)
Electrocardiogram QT prolonged	3/60 (5%)
Weight decreased	11/60 (18.3%)
Blood alkaline phosphatase increased	3/60 (5%)
Platelet count decreased	3/60 (5%)
Metabolism and nutrition disorders
Decreased appetite	18/60 (30%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/60 (11.7%)
Back pain	6/60 (10%)
Bone pain	7/60 (11.7%)
Myalgia	5/60 (8.3%)
Pain in extremity	6/60 (10%)
Nervous system disorders
Dysgeusia	27/60 (45%)
Headache	18/60 (30%)
Paraesthesia	4/60 (6.7%)
Peripheral sensory neuropathy	4/60 (6.7%)
Psychiatric disorders
Anxiety	7/60 (11.7%)
Depression	5/60 (8.3%)
Insomnia	9/60 (15%)
Renal and urinary disorders
Chromaturia	4/60 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	5/60 (8.3%)
Dyspnoea	9/60 (15%)
Epistaxis	18/60 (30%)
Oropharyngeal pain	4/60 (6.7%)
Dysphonia	3/60 (5%)
Skin and subcutaneous tissue disorders
Acne	7/60 (11.7%)
Dry skin	15/60 (25%)
Erythema	6/60 (10%)
Hair colour changes	7/60 (11.7%)
Palmar-plantar erythrodysaesthesia syndrome	10/60 (16.7%)
Rash	9/60 (15%)
Skin discolouration	3/60 (5%)
Yellow skin	13/60 (21.7%)
Pruritus	5/60 (8.3%)
Vascular disorders
Haematoma	3/60 (5%)
Hot flush	4/60 (6.7%)
Hypertension	25/60 (41.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.