Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00616122
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 81.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sunitinib when given together with cyclophosphamide and methotrexate to see how well they work in treating patients with metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: cyclophosphamide; Drug: methotrexate; Drug: sunitinib malate; Other: laboratory biomarker analysis	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of the combination of metronomic dose cyclophosphamide and methotrexate with continuous dosing sunitinib malate. (Phase I)

• To determine the time to disease progression in patients with metastatic breast cancer treated with metronomic dose chemotherapy with cyclophosphamide and methotrexate combined with continuous dosing of sunitinib malate. (Phase II)

Secondary

• To determine the response rate in patients receiving this treatment.

• To determine the duration of response in patients receiving this treatment.

• To determine the toxicity of this regimen in these patients.

• To determine the feasibility by assessment of toxicities of this regimen and number of voluntary withdrawals from the study.

• To correlate outcome measures with possible surrogate markers including serial measurements of circulating tumor cells and circulating endothelial cells.

OUTLINE: This is a dose-escalation study of sunitinib malate.

• Phase I: Patients receive oral sunitinib malate once daily. Beginning 14 days later, patients also receive oral cyclophosphamide once daily on days 1-21 and oral methotrexate twice daily on days 1, 2, 8, 9, 15, and 16. Treatment with sunitinib malate, cyclophosphamide, and methotrexate repeats every 21 days* in the absence of disease progression or unacceptable toxicity.

• Phase II: Patients receive sunitinib malate at the maximum tolerated dose determined in phase I and cyclophosphamide and methotrexate as in phase I.

NOTE: *Course 1 includes 2 weeks of sunitinib malate alone followed by sunitinib malate, cyclophosphamide, and methotrexate for 21 days

Blood samples are collected periodically for measurement of circulating tumor cells, circulating endothelial cells, and vascular endothelial growth factor (VEGF) levels.

After completion of study treatment, patients are followed for 30 days and then every 2 months for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer
• Actual Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sunitinib, Cyclophosphamide, and Methotrexate	Drug: cyclophosphamide; Drug: methotrexate; Drug: sunitinib malate; Other: laboratory biomarker analysis

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Sunitinib (Phase I) [8 weeks]

   Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature > 38.5 degrees Celsius or 3 readings of oral temperature > 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.

2. Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II) [up to 12 weeks after treatment start date]

   Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).

Secondary Outcome Measures

1. Overall Response Rate [until disease progression, up to 13 months post treatment]

   Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression.

2. Duration of Response [until disease progression up to 13 months post treatment]

   Duration of response refers to duration of single partial response observed per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression. Progression: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), OR appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Pathologically confirmed diagnosis of breast cancer with documented progressive disease

• Metastatic disease

• Measurable disease as defined by RECIST criteria or evaluable disease

• Must have received at least one prior chemotherapy regimen for metastatic breast cancer

• Patients refusing all other chemotherapy for breast cancer may enroll without prior treatment

• Patients with HER2-overexpression disease must have been previously treated with trastuzumab (Herceptin®)

• Patients with stable brain metastases are eligible

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Life expectancy ≥ 12 weeks

• Absolute Neutrophil Count (ANC) ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

• Total bilirubin ≤ 1.5 times ULN

• Able to take oral medications and maintain hydration

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after treatment

• No severe concurrent illness including, but not limited to, any of the following:

• Congestive heart failure

• Significant cardiac disease

• Uncontrolled hypertension

• Must be able to read and speak English

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 weeks since prior treatment, including chemotherapy, hormonal therapy, trastuzumab (Herceptin®), or other targeted therapies

• Prior bevacizumab allowed if discontinued for any reason other than toxicity

• No potent inducers or inhibitors of CYP3A4 enzymes that effect the metabolism of sunitinib malate

• No prior sunitinib malate

• No other concurrent investigational therapy

• No concurrent radiotherapy

• Concurrent bisphosphonates allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94115

Sponsors and Collaborators

• University of California, San Francisco
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Hope S. Rugo, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00616122
• Other Study ID Numbers: 057519; NCI-2011-01275
• First Posted: Feb 15, 2008
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of California, San Francisco: recurrent breast cancer; stage IV breast cancer; male breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Cyclophosphamide; Methotrexate; Sunitinib

Study Results

Participant Flow

Pre-assignment Detail	Phase I patients received escalating doses of sunitinib in a 3x3 design. None of the patients in the phase I study was included in phase II. Phase I patients receiving treatment at the phase II dose were included in the overall efficacy analysis of the phase II study but were not counted toward the enrollment accrual of the phase II study.

Arm/Group Title	Phase I, Dose 1	Phase I, Dose 2	Phase I, Dose 3	Phase II
Arm/Group Description	One cycle = 21 days Sunitinib only (12.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg twice a day (BID) 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.	One cycle = 21 days Sunitinib only (25 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.	One cycle = 21 days Sunitinib only (37.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.	37.5mg sunitinib during the 2-week lead-in period followed by either: 37.5mg sunitinib metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week)(CM) 25mg sunitinib metronomic CM (50mg/day) methotrexate (2.5mg BID 2 days/week)
Period Title: Overall Study
STARTED	4	7	10	11
COMPLETED	4	7	10	0
NOT COMPLETED	0	0	0	11

Baseline Characteristics

Arm/Group Title	Sunitinib, Cyclophosphamide, and Methotrexate
Arm/Group Description	Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	23 71.9%
>=65 years	9 28.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (15)
Sex: Female, Male (Count of Participants)
Female	31 96.9%
Male	1 3.1%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Sunitinib (Phase I)
Description	Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature > 38.5 degrees Celsius or 3 readings of oral temperature > 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib, Cyclophosphamide, and Methotrexate
Arm/Group Description	Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
Measure Participants	21
Number [mg]	37.5

2. Primary Outcome

Title	Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)
Description	Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Time Frame	up to 12 weeks after treatment start date

Outcome Measure Data

Analysis Population Description

Patients who received either 25mg or 37.5mg of sunitinib and were not removed from study due to voluntary withdrawal or PD prior to receiving combination sunitinib and metronomic CM chemotherapy.

Arm/Group Title	Sunitinib, Cyclophosphamide, and Methotrexate
Arm/Group Description	Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
Measure Participants	23
Number [participants]	7 21.9%

3. Secondary Outcome

Title	Overall Response Rate
Description	Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression.
Time Frame	until disease progression, up to 13 months post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib, Cyclophosphamide, and Methotrexate
Arm/Group Description	Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
Measure Participants	23
Number [participants]	1 3.1%

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response refers to duration of single partial response observed per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression. Progression: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), OR appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Time Frame	until disease progression up to 13 months post treatment

Outcome Measure Data

Analysis Population Description

A partial response was only reported for one patient, while a complete response was not recorded for any patients.

Arm/Group Title	Sunitinib, Cyclophosphamide, and Methotrexate
Arm/Group Description	Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
Measure Participants	1
Number [weeks]	10.6

Adverse Events

Arm/Group Title	Phase I, Dose 1		Phase I, Dose 2		Phase I, Dose 3		Phase II
Arm/Group Description	One cycle = 21 days Sunitinib only (12.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.		One cycle = 21 days Sunitinib only (25 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.		One cycle = 21 days Sunitinib only (37.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.		37.5mg sunitinib during the 2-week lead-in period followed by either: 37.5mg sunitinib metronomic CM (50mg/day) methotrexate (2.5mg BID 2 days/week) or 25mg sunitinib metronomic CM (50mg/day) methotrexate (2.5mg BID 2 days/week) (dose reduction due to a protocol amendment)
All Cause Mortality
	Phase I, Dose 1		Phase I, Dose 2		Phase I, Dose 3		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase I, Dose 1		Phase I, Dose 2		Phase I, Dose 3		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
fracture	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Phase I, Dose 1		Phase I, Dose 2		Phase I, Dose 3		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		6/7 (85.7%)		8/10 (80%)		11/11 (100%)
Blood and lymphatic system disorders
anemia	0/4 (0%)		2/7 (28.6%)		5/10 (50%)		7/11 (63.6%)
Cardiac disorders
impaired LV	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
sinus bradycardia	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
sinus tachycardia	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
Ear and labyrinth disorders
ear pain	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		1/11 (9.1%)
pulsing in ear	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
vertigo	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
Eye disorders
dry eyes	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
floaters	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
heavy eyelid	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
puffy eyelid	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
Gastrointestinal disorders
abdominal distention	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
abdominal pain	0/4 (0%)		0/7 (0%)		1/10 (10%)		2/11 (18.2%)
anal pain	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
ascites	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
cold sore	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
constipation	0/4 (0%)		0/7 (0%)		3/10 (30%)		2/11 (18.2%)
diarrhea	0/4 (0%)		2/7 (28.6%)		7/10 (70%)		5/11 (45.5%)
dry mouth	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
dry mucous membrane	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
dysgeusia	0/4 (0%)		1/7 (14.3%)		2/10 (20%)		3/11 (27.3%)
dyspepsia	0/4 (0%)		1/7 (14.3%)		1/10 (10%)		0/11 (0%)
gastroesophageal reflux disorder	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		1/11 (9.1%)
gastrotitis	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
mucositis oral	0/4 (0%)		5/7 (71.4%)		1/10 (10%)		2/11 (18.2%)
nausea	1/4 (25%)		2/7 (28.6%)		5/10 (50%)		4/11 (36.4%)
oral pain	0/4 (0%)		0/7 (0%)		3/10 (30%)		1/11 (9.1%)
rectal hemorrhage	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
vomiting	0/4 (0%)		1/7 (14.3%)		3/10 (30%)		4/11 (36.4%)
General disorders
chills	0/4 (0%)		1/7 (14.3%)		1/10 (10%)		2/11 (18.2%)
edema limbs	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		2/11 (18.2%)
fatigue	0/4 (0%)		5/7 (71.4%)		7/10 (70%)		7/11 (63.6%)
fever	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		4/11 (36.4%)
non-cardiac chest pain	0/4 (0%)		0/7 (0%)		0/10 (0%)		2/11 (18.2%)
pain	0/4 (0%)		0/7 (0%)		3/10 (30%)		0/11 (0%)
Hepatobiliary disorders
jaundice	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
Immune system disorders
allergic reaction	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
Infections and infestations
bacterial vaginosis	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
breast infection	1/4 (25%)		0/7 (0%)		0/10 (0%)		0/11 (0%)
sinusitis	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
upper respiratory infection	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
urinary tract infection	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
Injury, poisoning and procedural complications
bruising	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
fall	1/4 (25%)		0/7 (0%)		0/10 (0%)		0/11 (0%)
spider bite	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
Investigations
activated partial thromboplastin time prolonged	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
alanine aminotransferase increased	2/4 (50%)		0/7 (0%)		2/10 (20%)		4/11 (36.4%)
alkaline phosphatase increased	2/4 (50%)		0/7 (0%)		2/10 (20%)		4/11 (36.4%)
aspartate aminotransferase increased	2/4 (50%)		0/7 (0%)		4/10 (40%)		6/11 (54.5%)
blood blirubin increased	0/4 (0%)		0/7 (0%)		2/10 (20%)		2/11 (18.2%)
blood urea nitrogen increased	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
creatinine increased	0/4 (0%)		0/7 (0%)		0/10 (0%)		3/11 (27.3%)
lymphocyte count decreased	0/4 (0%)		0/7 (0%)		5/10 (50%)		3/11 (27.3%)
neutrophil count decreased	0/4 (0%)		6/7 (85.7%)		8/10 (80%)		9/11 (81.8%)
platelet count decreased	0/4 (0%)		3/7 (42.9%)		4/10 (40%)		9/11 (81.8%)
weight loss	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
white blood cell decreased	0/4 (0%)		0/7 (0%)		6/10 (60%)		6/11 (54.5%)
Metabolism and nutrition disorders
anorexia	1/4 (25%)		4/7 (57.1%)		3/10 (30%)		1/11 (9.1%)
hyperglycemia	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
hypoalbuminemia	0/4 (0%)		0/7 (0%)		1/10 (10%)		1/11 (9.1%)
hypocalcemia	0/4 (0%)		0/7 (0%)		2/10 (20%)		1/11 (9.1%)
hypochloremia	0/4 (0%)		0/7 (0%)		0/10 (0%)		2/11 (18.2%)
hypokalemia	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
hyponatremia	0/4 (0%)		0/7 (0%)		1/10 (10%)		2/11 (18.2%)
Musculoskeletal and connective tissue disorders
arthralgia	0/4 (0%)		1/7 (14.3%)		1/10 (10%)		0/11 (0%)
back pain	0/4 (0%)		2/7 (28.6%)		1/10 (10%)		3/11 (27.3%)
generalized muscle weakness	0/4 (0%)		0/7 (0%)		1/10 (10%)		1/11 (9.1%)
groin pain	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
hip pain	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
myalgia	1/4 (25%)		4/7 (57.1%)		0/10 (0%)		3/11 (27.3%)
myositis	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
neck pain	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
pain in extremity	0/4 (0%)		1/7 (14.3%)		1/10 (10%)		5/11 (45.5%)
rib pain	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		1/11 (9.1%)
Nervous system disorders
cognitive disturbance	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
dizziness	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		1/11 (9.1%)
hand stiffness	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
headache	0/4 (0%)		0/7 (0%)		3/10 (30%)		3/11 (27.3%)
lightheadedness	1/4 (25%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
loss of function in right hand	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
numbness to chin	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
peripheral motor neuropathy	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
peripheral sensory neuropathy	0/4 (0%)		2/7 (28.6%)		4/10 (40%)		3/11 (27.3%)
Psychiatric disorders
anxiety	0/4 (0%)		2/7 (28.6%)		0/10 (0%)		2/11 (18.2%)
depression	0/4 (0%)		0/7 (0%)		1/10 (10%)		1/11 (9.1%)
insomnia	0/4 (0%)		0/7 (0%)		1/10 (10%)		2/11 (18.2%)
Renal and urinary disorders
urinary incontinence	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
cough	0/4 (0%)		1/7 (14.3%)		3/10 (30%)		3/11 (27.3%)
dullness in lungs	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
dyspnea	0/4 (0%)		0/7 (0%)		2/10 (20%)		1/11 (9.1%)
epistaxis	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
esophagoscopy abnormal	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
hoarseness	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		1/11 (9.1%)
sore throat	0/4 (0%)		3/7 (42.9%)		0/10 (0%)		0/11 (0%)
voice alteration	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
Skin and subcutaneous tissue disorders
alopecia	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
desquamation, blistering	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
dry skin	1/4 (25%)		2/7 (28.6%)		0/10 (0%)		1/11 (9.1%)
erythema	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
hyperpigmentation	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
palmar-plantar erythrodysesthesia syndrome	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
petechia	0/4 (0%)		2/7 (28.6%)		0/10 (0%)		0/11 (0%)
pruritus	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
psoriasis	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
rash	0/4 (0%)		0/7 (0%)		1/10 (10%)		2/11 (18.2%)
skin peeling	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)
warmth to chest wall	0/4 (0%)		0/7 (0%)		1/10 (10%)		0/11 (0%)
Vascular disorders
hot flashes	1/4 (25%)		0/7 (0%)		0/10 (0%)		0/11 (0%)
hypertension	0/4 (0%)		0/7 (0%)		2/10 (20%)		3/11 (27.3%)
night sweats	0/4 (0%)		0/7 (0%)		0/10 (0%)		1/11 (9.1%)
thromboembolic event	0/4 (0%)		1/7 (14.3%)		0/10 (0%)		0/11 (0%)

Limitations/Caveats

Based on published literature indicating significant toxicity and low response rate for combination sunitinib in the treatment of advanced breast cancer, the PI and Breast Oncology Site Committee closed enrollment after accrual of 32 participants.

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Certain Agreements

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

There is NOT 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.