Study Of SU011248 In Combination With Docetaxel And Trastuzumab In Patients With Advanced Breast Cancer HER-2 Positive

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00372424
• Collaborator: (none)
• Enrollment: 26
• Locations: 7
• Arm: 1
• Duration (Months): 57
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an exploratory trial evaluating the tolerability and preliminary anti-tumor activity of SU011248 combined with docetaxel and trastuzumab in patients with locally recurrent or metastatic breast cancer over-expressing Her-2, who have not received chemotherapy treatment in the advanced disease setting.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Herceptin; Drug: Sunitinib; Drug: Taxotere	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Explorative Study Of The Tolerability Of SU011248 In Combination With Docetaxel And Trastuzumab As First-Line Treatment In Patients With Breast Cancer Over-Expressing HER-2
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1 Combination of SU011248 (37.5 mg once daily [Schedule 2/1]) with docetaxel (75 mg/m2 every 3 weeks) and trastuzumab (therapeutic dose)

Drug: Herceptin; Trastuzumab will be administered intravenously on Day 1 before docetaxel - loading dose of 4 mg/kg over 90-minute on Day 1 followed by weekly maintenance doses of 2 mg/kg on Days 1, 8, 15 given as 30-minute infusions if the initial loading dose was well tolerated. Loading dose of 8 mg/kg over 90-minute on Day 1 followed by 3-weekly maintenance doses of 6 mg/kg given as 90-minute infusions. The administration of 6 mg/kg will be repeated on Day 1 every 3 weeks.; Other Names: trastuzumab ; Drug: Sunitinib; SU011248 will be administered at 37.5 mg once daily for 2 weeks every 3 weeks (Schedule 2/1) starting from Day 2, when in combination with docetaxel. SU011248 will be administered at the starting dose of 37.5 mg daily in a continuous regimen when docetaxel is discontinued.; Other Names: Sutent ; Drug: Taxotere; The starting dose of docetaxel will be 75 mg/m2 every 3 weeks, administered on Day 1 of each cycle as a 1-hour IV infusion.; Other Names: docetaxel

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [From screening until 28 days post last dose of study drug]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (OR) [Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)]

   Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all target lesions. PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

2. Progression-free Survival (PFS) [Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)]

   Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

3. Duration of Response (DR) [Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)]

   Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

4. Plasma Trough Concentrations (Ctrough) of SU011248 (Sunitinib), SU012662 (Sunitinib Metabolite) and Total Drug (SU011248+SU012662) [Pre-dose (0 hours [H]) on Day 1 and Day 15 of Cycle 2, 4, 6 and additionally Day 15 of Cycle 1]

   Ctrough = the concentration prior to study medication administration. Ctrough was calculated for SU011248 (Sunitinib), SU012662 (Sunitinib metabolite) and total drug (SU011248+SU012662). Concentration values below the lower limit of quantification were taken as zero.

5. Maximum Observed Plasma Concentration (Cmax) of Docetaxel [End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6]

   Concentration values below the lower limit of quantification were taken as zero.

6. Plasma Trough Concentrations (Ctrough) of Trastuzumab [Weekly trastuzumab: Pre-dose (0 H) on Day 1 and 15 of Cycle 1, 2, 4 and 6; 3-weekly trastuzumab: Pre-dose (0 H) on Day 1 of Cycle 1, 2, 4 and 6]

   Ctrough = the concentration prior to study medication administration.

Other Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Paclitaxel [End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Breast cancer with evidence of unresectable, locally recurrent, or metastatic disease.

• Tumors over-expressing Her-2

• Candidate for treatment with docetaxel/trastuzumab

Exclusion Criteria:

• Histology of inflammatory carcinoma

• AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bruxelles		Belgium	1000
2	Pfizer Investigational Site	Bruxelles		Belgium	1200
3	Pfizer Investigational Site	Charleroi		Belgium	6000
4	Pfizer Investigational Site	Sint-Niklaas		Belgium	9100
5	Pfizer Investigational Site	Wilrijk		Belgium	2610
6	Pfizer Investigational Site	Meldola	FC	Italy	47014
7	Pfizer Investigational Site	Milano		Italy	20132

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00372424
• Other Study ID Numbers: A6181113
• First Posted: Sep 7, 2006
• Last Update Posted: Dec 28, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by Pfizer: Breast cancer over-expressing HER2. First-line treatment with sunitinib/docetaxel/trastuzumab.
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel; Trastuzumab; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Period Title: Overall Study
STARTED	26
Treated	25
COMPLETED	0
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.0 (12.8)
Sex: Female, Male (Count of Participants)
Female	25 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	From screening until 28 days post last dose of study drug

Outcome Measure Data

Analysis Population Description

Safety population included all participants enrolled in the study who received at least 1 dose of study medication.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	25
AEs	24 96%
SAEs	11 44%

2. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all target lesions. PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)

Outcome Measure Data

Analysis Population Description

Per protocol (PP) population included all participants who received at least 1 dose of sunitinib and had at least a tumor assessment post baseline.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	22
Number (95% Confidence Interval) [percentage of participants]	72.7 290.8%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame	Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)

Outcome Measure Data

Analysis Population Description

Study population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	25
Median (95% Confidence Interval) [weeks]	58.4

4. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)

Outcome Measure Data

Analysis Population Description

Study population, subgroup of participants with a confirmed objective tumor response (CR or PR).

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	16
Median (95% Confidence Interval) [weeks]	51.3

5. Secondary Outcome

Title	Plasma Trough Concentrations (Ctrough) of SU011248 (Sunitinib), SU012662 (Sunitinib Metabolite) and Total Drug (SU011248+SU012662)
Description	Ctrough = the concentration prior to study medication administration. Ctrough was calculated for SU011248 (Sunitinib), SU012662 (Sunitinib metabolite) and total drug (SU011248+SU012662). Concentration values below the lower limit of quantification were taken as zero.
Time Frame	Pre-dose (0 hours [H]) on Day 1 and Day 15 of Cycle 2, 4, 6 and additionally Day 15 of Cycle 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set included participants from study population who had completed sampling for pharmacokinetic profiles for study medication. 'n' is number of participants who were evaluable at given time points.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	25
Sunitinib: Cycle1/Day15 (n= 19)	40.17 (32.17)
Sunitinib: Cycle2/Day1 (n= 17)	5.96 (6.17)
Sunitinib: Cycle2/Day15 (n= 16)	37.29 (31.07)
Sunitinib: Cycle4/Day1 (n= 17)	5.26 (5.71)
Sunitinib: Cycle4/Day15 (n= 16)	43.21 (27.31)
Sunitinib: Cycle6/Day1 (n= 16)	3.36 (4.34)
Sunitinib: Cycle6/Day15 (n= 13)	28.46 (21.19)
Sunitinib Metabolite: Cycle1/Day15 (n= 19)	16.15 (12.09)
Sunitinib Metabolite: Cycle2/Day1 (n= 17)	4.76 (3.92)
Sunitinib Metabolite: Cycle2/Day15 (n= 16)	14.43 (11.34)
Sunitinib Metabolite: Cycle4/Day1 (n= 17)	3.95 (2.57)
Sunitinib Metabolite: Cycle4/Day15 (n= 16)	17.62 (11.17)
Sunitinib Metabolite: Cycle6/Day1 (n= 16)	2.96 (2.89)
Sunitinib Metabolite: Cycle6/Day15 (n= 13)	11.54 (9.66)
Total Drug: Cycle1/Day15 (n= 19)	56.31 (42.70)
Total Drug: Cycle2/Day1 (n= 17)	10.72 (9.80)
Total Drug: Cycle2/Day15 (n= 16)	51.72 (41.45)
Total Drug: Cycle4/Day1 (n= 17)	9.21 (7.97)
Total Drug: Cycle4/Day15 (n= 16)	60.83 (37.43)
Total Drug: Cycle6/Day1 (n= 16)	6.32 (7.02)
Total Drug: Cycle6/Day15 (n= 13)	40.00 (30.04)

6. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Docetaxel
Description	Concentration values below the lower limit of quantification were taken as zero.
Time Frame	End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6

Outcome Measure Data

Analysis Population Description

PK analysis set included participants from study population who had completed sampling for pharmacokinetic profiles for study medication. 'n' is number of participants who were evaluable at given time points.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	25
Cycle1/Day1 (n= 23)	1117.05 (1159.53)
Cycle2/Day1 (n= 19)	1388.63 (1260.94)
Cycle4/Day1 (n= 16)	1316.88 (1096.97)
Cycle6/Day1 (n= 15)	1670.40 (1614.07)

7. Secondary Outcome

Title	Plasma Trough Concentrations (Ctrough) of Trastuzumab
Description	Ctrough = the concentration prior to study medication administration.
Time Frame	Weekly trastuzumab: Pre-dose (0 H) on Day 1 and 15 of Cycle 1, 2, 4 and 6; 3-weekly trastuzumab: Pre-dose (0 H) on Day 1 of Cycle 1, 2, 4 and 6

Outcome Measure Data

Analysis Population Description

Data was not summarized since majority of observed Ctrough values were below lower limit of quantification.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	0

8. Other Pre-specified Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Paclitaxel
Time Frame	End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6

Outcome Measure Data

Analysis Population Description

Data not analyzed since paclitaxel was not administered in the study.

Arm/Group Title	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
Measure Participants	0

Adverse Events

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	Sunitinib + Docetaxel + Trastuzumab
Arm/Group Description	Sunitinib 37.5 milligram (mg) capsule orally once daily continuously starting from Day 2 up to Day 15 in each cycle, in schedule 2/1 (2 week on treatment, 1 week off treatment) along with docetaxel 75 milligram/square meter (mg/m^2) intravenous infusion over 1 hour on Day 1 of each cycle and trastuzumab either weekly: loading dose of 4 milligram/kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 followed by weekly maintenance doses of 2 mg/kg intravenous infusion over 30 minutes; or every 3 weeks: loading dose of 8 mg/kg intravenous infusion over 90 minutes on Day 1 followed by maintenance doses of 6 mg/kg intravenous infusion over 90 minutes every 3 weeks. Cycle length was 3 weeks.
All Cause Mortality
	Sunitinib + Docetaxel + Trastuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib + Docetaxel + Trastuzumab
	Affected / at Risk (%)	# Events
Total	11/25 (44%)
Blood and lymphatic system disorders
Febrile neutropenia	4/25 (16%)
Neutropenia	3/25 (12%)
Gastrointestinal disorders
Diarrhoea	1/25 (4%)
Intestinal perforation	1/25 (4%)
Rectal haemorrhage	1/25 (4%)
Stomatitis	1/25 (4%)
Vomiting	1/25 (4%)
General disorders
Fatigue	1/25 (4%)
Multi-organ failure	1/25 (4%)
Infections and infestations
Erysipelas	1/25 (4%)
Pseudomembranous colitis	1/25 (4%)
Sepsis	1/25 (4%)
Viral infection	1/25 (4%)
Musculoskeletal and connective tissue disorders
Pathological fracture	1/25 (4%)
Nervous system disorders
Syncope	1/25 (4%)
Psychiatric disorders
Anxiety	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/25 (4%)
Lung disorder	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Sunitinib + Docetaxel + Trastuzumab
	Affected / at Risk (%)	# Events
Total	23/25 (92%)
Blood and lymphatic system disorders
Anaemia	6/25 (24%)
Febrile neutropenia	2/25 (8%)
Leukopenia	6/25 (24%)
Neutropenia	14/25 (56%)
Thrombocytopenia	4/25 (16%)
Eye disorders
Conjunctivitis	5/25 (20%)
Lacrimation increased	2/25 (8%)
Gastrointestinal disorders
Abdominal pain	4/25 (16%)
Abdominal pain upper	7/25 (28%)
Constipation	4/25 (16%)
Diarrhoea	15/25 (60%)
Dyspepsia	2/25 (8%)
Haemorrhoids	3/25 (12%)
Nausea	11/25 (44%)
Stomatitis	7/25 (28%)
Vomiting	7/25 (28%)
General disorders
Asthenia	4/25 (16%)
Fatigue	15/25 (60%)
Mucosal inflammation	4/25 (16%)
Oedema	2/25 (8%)
Oedema peripheral	6/25 (24%)
Pyrexia	13/25 (52%)
Immune system disorders
Drug hypersensitivity	3/25 (12%)
Hypersensitivity	2/25 (8%)
Infections and infestations
Bronchitis	2/25 (8%)
Cystitis	2/25 (8%)
Gastroenteritis viral	2/25 (8%)
Pharyngitis	2/25 (8%)
Sinusitis	2/25 (8%)
Investigations
Weight decreased	2/25 (8%)
Metabolism and nutrition disorders
Decreased appetite	6/25 (24%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/25 (20%)
Back pain	6/25 (24%)
Bone pain	3/25 (12%)
Myalgia	8/25 (32%)
Nervous system disorders
Dizziness	2/25 (8%)
Dysgeusia	4/25 (16%)
Headache	4/25 (16%)
Paraesthesia	3/25 (12%)
Peripheral sensory neuropathy	4/25 (16%)
Respiratory, thoracic and mediastinal disorders
Cough	7/25 (28%)
Dyspnoea	4/25 (16%)
Epistaxis	9/25 (36%)
Oropharyngeal pain	5/25 (20%)
Skin and subcutaneous tissue disorders
Acne	2/25 (8%)
Alopecia	6/25 (24%)
Dermatitis	2/25 (8%)
Hair colour changes	2/25 (8%)
Palmar-plantar erythrodysaesthesia syndrome	6/25 (24%)
Rash	5/25 (20%)
Skin discolouration	2/25 (8%)
Vascular disorders
Hypertension	6/25 (24%)
Phlebitis	2/25 (8%)

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.