A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B)

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00434356
• Collaborator: (none)
• Enrollment: 46
• Arms: 2

Study Details

Study Description

Brief Summary

This is a multicenter, Phase II, randomized, controlled, open label trial designed to provide a preliminary assessment of the safety and efficacy of sunitinib when combined with bevacizumab and paclitaxel in patients who have not previously received chemotherapy for locally recurrent or metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: bevacizumab; Drug: sunitinib; Drug: paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Phase II, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: bevacizumab; Intravenous repeating dose; Drug: sunitinib; Oral repeating dose; Drug: paclitaxel; Intravenous repeating dose
Placebo Comparator: 2	Drug: bevacizumab; Intravenous repeating dose; Drug: paclitaxel; Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

1. Best Response [From randomization until disease progression/recurrence (by patient)]

   The best overall response is the best response, per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome.

Secondary Outcome Measures

1. Serious Adverse Events (SAEs) [30 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. An SAE is defined as an adverse event that results in death, is life threatening, requires hospitalization, results in significant disability, results in birth defect, or is considered a significant medical event by the investigator

2. Grade ≥ 3 Adverse Events (AEs) [30 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Grading: 1=Mild AE; 2=Moderate AE; 3=Severe AE; 4=Life-threatening or disabling AE; 5=Death related to AE

3. Adverse Events Leading to Death [30 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

4. Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction [30 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

5. Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption [30 days following the last administration of study treatment]

   All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed Informed Consent Form

• Histologically or cytologically confirmed adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease

• Age ≥ 18 years

• Adequate left ventricular function at study entry, defined as an Left Ventricular Ejection Fraction (LVEF) > 50% by either Multi Gated Acquisition(MUGA) scan or Electrocardiogram (ECHO)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Ability and willingness to comply with study and follow-up procedures

Exclusion Criteria:

• Unknown HER2 status or known HER2-positive status

• Prior chemotherapy for locally recurrent or metastatic disease

• Prior hormonal therapy within 2 weeks prior to Day 1

• Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior to Day 1

• Prior adjuvant or neoadjuvant non-taxane chemotherapy within 6 months prior to Day 1

• For patients who have received recent radiotherapy, ongoing Grade ≥ 3 acute toxicity

• Patients with brain metastasis on full dose anticoagulation therapy

• Life expectancy of < 12 weeks

• Current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study

• Inadequate organ function within 28 days prior to Day 1

• Untreated abnormal thyroid function tests

• Uncontrolled serious medical or psychiatric illness

• Active infection requiring IV antibiotics at enrollment or randomization

• History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix

• Inadequately controlled hypertension

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association (NYHA) Class II or greater CHF

• History of myocardial infarction or unstable angina within 12 months prior to Day 1

• History of stroke or transient ischemic attack within 12 months prior to Day 1

• Known central nervous system (CNS) disease except for treated brain metastasis

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1

• History of hemoptysis within 1 month prior to Day 1

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1

• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

• Serious, non-healing wound, active ulcer, or untreated bone fracture

• Proteinuria at screening, as demonstrated by a urine protein/creatinine ratio of ≥ 1.0 at screening

• Known hypersensitivity to any component of bevacizumab or sunitinib

• Pregnancy (positive pregnancy test) or lactation

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Jai Balkissoon, M.D., Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00434356
• Other Study ID Numbers: AVF4057g
• First Posted: Feb 13, 2007
• Last Update Posted: Dec 3, 2009
• Last Verified: Nov 1, 2009

• Keywords provided by , ,: Avastin; MBC; Breast Cancer; Sutent
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Bevacizumab; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Period Title: Overall Study
STARTED	23	23
COMPLETED	0	0
NOT COMPLETED	23	23

Baseline Characteristics

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel	Total
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest	Total of all reporting groups
Overall Participants	23	23	46
Age, Customized (participants) [Number]
< 18 Years	0 0%	0 0%	0 0%
Between 18 and 40 Years	2 8.7%	5 21.7%	7 15.2%
Between 41 and 64 Years	15 65.2%	17 73.9%	32 69.6%
>= 65 Years	6 26.1%	1 4.3%	7 15.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (13.3)	50.8 (11.7)	54 (12.8)
Sex: Female, Male (Count of Participants)
Female	23 100%	23 100%	46 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Best Response
Description	The best overall response is the best response, per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome.
Time Frame	From randomization until disease progression/recurrence (by patient)

Outcome Measure Data

Analysis Population Description

Randomized patients with at least one scan available at baseline and post-baseline

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Measure Participants	17	18
Complete Response	0 0%	0 0%
Partial Response	12 52.2%	11 47.8%
Stable Disease	3 13%	4 17.4%
Progressive Disease	2 8.7%	2 8.7%
Unable to Evaluate	0 0%	1 4.3%
Missing	0 0%	0 0%

2. Secondary Outcome

Title	Serious Adverse Events (SAEs)
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. An SAE is defined as an adverse event that results in death, is life threatening, requires hospitalization, results in significant disability, results in birth defect, or is considered a significant medical event by the investigator
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Measure Participants	23	23
Febrile Neutropenia	2 8.7%	1 4.3%
Haemolytic Anaemia	1 4.3%	0 0%
Neutropenia	0 0%	1 4.3%
Constipation	1 4.3%	0 0%
Diarrhoea	1 4.3%	0 0%
Gastrointestinal Perforation	1 4.3%	0 0%
Haemorrhoids	1 4.3%	0 0%
Vomiting	1 4.3%	0 0%
Chest Pain	0 0%	2 8.7%
Asthenia	0 0%	1 4.3%
Anaphylactic Reaction	1 4.3%	0 0%
Drug Hypersensitivity	0 0%	1 4.3%
Upper Respiratory Tract Infection	0 0%	2 8.7%
Cellulitis	0 0%	1 4.3%
Pneumonia	0 0%	1 4.3%
Tooth Infection	1 4.3%	0 0%
Spinal Compression Fracture	1 4.3%	0 0%
Dehydration	1 4.3%	2 8.7%
Hypoglycaemi	0 0%	1 4.3%
Syncope	0 0%	1 4.3%
Pulmonary Embolism	1 4.3%	1 4.3%
Epistaxis	0 0%	1 4.3%
Hypoxia	0 0%	1 4.3%
Skin Ulcer	1 4.3%	0 0%

3. Secondary Outcome

Title	Grade ≥ 3 Adverse Events (AEs)
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Grading: 1=Mild AE; 2=Moderate AE; 3=Severe AE; 4=Life-threatening or disabling AE; 5=Death related to AE
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Measure Participants	23	23
Neutropenia	10 43.5%	2 8.7%
Leukopenia	7 30.4%	0 0%
Febrile Neutropenia	3 13%	1 4.3%
Haemolytic Anaemia	1 4.3%	0 0%
Lymphopenia	1 4.3%	0 0%
Diarrhoea	4 17.4%	0 0%
Constipation	0 0%	1 4.3%
Nausea	1 4.3%	0 0%
Vomiting	1 4.3%	0 0%
Gastrointestinal Perforation	1 4.3%	0 0%
Haemorrhoids	1 4.3%	0 0%
Small Intestinal Obstruction	1 4.3%	0 0%
Fatigue	6 26.1%	2 8.7%
Chest Pain	0 0%	2 8.7%
Asthenia	0 0%	1 4.3%
Mucosal Inflammation	0 0%	1 4.3%
Hyperbilirubinaemia	1 4.3%	0 0%
Drug Hypersensitivity	2 8.7%	1 4.3%
Anaphylactic Reaction	1 4.3%	0 0%
Upper Respiratory Tract Infection	0 0%	2 8.7%
Cellulitis	0 0%	1 4.3%
Otitis Media	1 4.3%	0 0%
Pneumonia	0 0%	1 4.3%
Tooth Infection	1 4.3%	0 0%
Urinary Tract Infection	0 0%	1 4.3%
Spinal Compression Fracture	1 4.3%	0 0%
Thermal Burn	1 4.3%	0 0%
Haemoglobin Decreased	0 0%	1 4.3%
Neutrophil Count Decreased	0 0%	1 4.3%
Dehydration	1 4.3%	2 8.7%
Anorexia	1 4.3%	0 0%
Hypoglycaemia	0 0%	1 4.3%
Neuropathy Peripheral	1 4.3%	2 8.7%
Headache	1 4.3%	0 0%
Migraine	0 0%	1 4.3%
Syncope	0 0%	1 4.3%
Haematuria	1 4.3%	0 0%
Epistaxis	0 0%	1 4.3%
Pulmonary Embolism	1 4.3%	1 4.3%
Palmar-Plantar Erythrodysaesthesia Syndrome	0 0%	1 4.3%
Skin Ulcer	1 4.3%	0 0%
Hypertension	2 8.7%	1 4.3%

4. Secondary Outcome

Title	Adverse Events Leading to Death
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Measure Participants	23	23
Number [participants]	0 0%	0 0%

5. Secondary Outcome

Title	Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest
Measure Participants	23
Neutropenia	11 47.8%
Leukopenia	6 26.1%
Febrile Neutropenia	2 8.7%
Thrombocytopenia	2 8.7%
Lymphopenia	1 4.3%
Diarrhoea	4 17.4%
Nausea	2 8.7%
Vomiting	2 8.7%
Constipation	1 4.3%
Gastrointestinal Perforation	1 4.3%
Haemorrhoids	1 4.3%
Hyperbilirubinaemia	1 4.3%
Anaphylactic Reaction	1 4.3%
Drug Hypersensitivity	1 4.3%
Otitis Media	1 4.3%
Tooth Infection	1 4.3%
Spinal Compression Fracture	1 4.3%
Thermal Burn	1 4.3%
Anorexia	1 4.3%
Dehydration	1 4.3%
Neuropathy Peripheral	1 4.3%
Haematuria	1 4.3%
Skin Ulcer	1 4.3%
Hypertension	2 8.7%

6. Secondary Outcome

Title	Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption
Description	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib	Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
Measure Participants	23	23
Neutropenia	9 39.1%	4 17.4%
Leukopenia	4 17.4%	0 0%
Febrile Neutropenia	2 8.7%	0 0%
Haemolytic Anaemia	1 4.3%	0 0%
Lymphopenia	1 4.3%	0 0%
Thrombocytopenia	1 4.3%	0 0%
Diarrhoea	3 13%	0 0%
Constipation	1 4.3%	0 0%
Gastrointestinal Perforation	1 4.3%	0 0%
Gingival Bleeding	1 4.3%	0 0%
Nausea	1 4.3%	0 0%
Small Intestinal Obstruction	1 4.3%	0 0%
Toothache	0 0%	1 4.3%
Vomiting	1 4.3%	0 0%
Fatigue	3 13%	3 13%
Chest Pain	0 0%	1 4.3%
Mucosal Inflammation	0 0%	1 4.3%
Hyperbilirubinaemia	1 4.3%	0 0%
Anaphylactic Reaction	1 4.3%	0 0%
Otitis Media	1 4.3%	0 0%
Pneumonia	0 0%	1 4.3%
Rhinitis	1 4.3%	0 0%
Skin Infection	1 4.3%	0 0%
Upper Respiratory Tract Infection	0 0%	1 4.3%
Thermal Burn	1 4.3%	0 0%
Dehydration	1 4.3%	2 8.7%
Anorexia	1 4.3%	1 4.3%
Hypoglycaemia	0 0%	1 4.3%
Neuropathy Peripheral	1 4.3%	1 4.3%
Memory Impairment	1 4.3%	0 0%
Migraine	0 0%	1 4.3%
Confusional State	1 4.3%	0 0%
Haematuria	1 4.3%	0 0%
Proteinuria	1 4.3%	0 0%
Epistaxis	1 4.3%	1 4.3%
Dyspnoea	0 0%	1 4.3%
Haemoptysis	0 0%	1 4.3%
Pulmonary Embolism	0 0%	1 4.3%
Dermatitis	0 0%	1 4.3%
Skin Ulcer	1 4.3%	0 0%
Hypertension	1 4.3%	0 0%

Adverse Events

Arm/Group Title	Bevacizumab + Paclitaxel + Sunitinib		Bevacizumab + Paclitaxel
Arm/Group Description	Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest; sunitinib will be administered orally at 25 mg/day or 37.5 mg/day for 3 weeks followed by 1 week of rest		Bevacizumab will be administered at 10 mg/kg by intravenous (IV) infusion every 2 weeks; paclitaxel will be administered at 90 mg/m2 by IV infusion weekly for 3 weeks followed by 1 week of rest
All Cause Mortality
	Bevacizumab + Paclitaxel + Sunitinib		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bevacizumab + Paclitaxel + Sunitinib		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/23 (43.5%)		9/23 (39.1%)
Blood and lymphatic system disorders
Febrile Neutropenia	2/23 (8.7%)		1/23 (4.3%)
Neutropenia	0/23 (0%)		1/23 (4.3%)
Hemolytic Anemia	1/23 (4.3%)		0/23 (0%)
Gastrointestinal disorders
Diarrhea	1/23 (4.3%)		0/23 (0%)
Constipation	1/23 (4.3%)		0/23 (0%)
Gastrointestinal Perforatioin	1/23 (4.3%)		0/23 (0%)
Hemorrhoids	1/23 (4.3%)		0/23 (0%)
Vomiting	1/23 (4.3%)		0/23 (0%)
General disorders
Chest Pain	0/23 (0%)		2/23 (8.7%)
Asthenia	0/23 (0%)		1/23 (4.3%)
Immune system disorders
Drug Hypersensitivity	0/23 (0%)		1/23 (4.3%)
Anaphylactic Reaction	1/23 (4.3%)		0/23 (0%)
Cellulitis	0/23 (0%)		1/23 (4.3%)
Tooth Infection	1/23 (4.3%)		0/23 (0%)
Infections and infestations
Upper Respiratory Tract Infection	0/23 (0%)		2/23 (8.7%)
Pneumonia	0/23 (0%)		1/23 (4.3%)
Injury, poisoning and procedural complications
Spinal Compression Fracture	1/23 (4.3%)		0/23 (0%)
Metabolism and nutrition disorders
Dehydration	1/23 (4.3%)		2/23 (8.7%)
Hypoglycemia	0/23 (0%)		1/23 (4.3%)
Nervous system disorders
Syncope	0/23 (0%)		1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/23 (4.3%)		1/23 (4.3%)
Hypoxia	0/23 (0%)		1/23 (4.3%)
Epistaxis	0/23 (0%)		1/23 (4.3%)
Skin and subcutaneous tissue disorders
Skin Ulcer	1/23 (4.3%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Bevacizumab + Paclitaxel + Sunitinib		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)		18/23 (78.3%)
Blood and lymphatic system disorders
Neutropenia	13/23 (56.5%)		5/23 (21.7%)
Leukopenia	7/23 (30.4%)		0/23 (0%)
Febrile Neutropenia	1/23 (4.3%)		0/23 (0%)
Thrombocytopenia	2/23 (8.7%)		0/23 (0%)
Lymphopenia	1/23 (4.3%)		0/23 (0%)
Cardiac disorders
Tachycardia	0/23 (0%)		1/23 (4.3%)
Gastrointestinal disorders
Diarrhoea	4/23 (17.4%)		1/23 (4.3%)
Nausea	3/23 (13%)		0/23 (0%)
Vomiting	2/23 (8.7%)		0/23 (0%)
Constipation	1/23 (4.3%)		1/23 (4.3%)
Gingival Bleeding	1/23 (4.3%)		0/23 (0%)
Small Intestinal Obstruction	1/23 (4.3%)		0/23 (0%)
Toothache	1/23 (4.3%)		1/23 (4.3%)
Oral Discomfort	1/23 (4.3%)		0/23 (0%)
Stomatitis	1/23 (4.3%)		0/23 (0%)
General disorders
Fatigue	8/23 (34.8%)		5/23 (21.7%)
Mucosal Inflammation	0/23 (0%)		1/23 (4.3%)
Pain	0/23 (0%)		1/23 (4.3%)
Pyrexia	0/23 (0%)		1/23 (4.3%)
Hepatobiliary disorders
Hyperbilirubinemia	1/23 (4.3%)		0/23 (0%)
Infections and infestations
Otitis Media	1/23 (4.3%)		0/23 (0%)
Rhinitis	1/23 (4.3%)		0/23 (0%)
Skin Infection	1/23 (4.3%)		0/23 (0%)
Urinary Tract Infection	0/23 (0%)		1/23 (4.3%)
Infection	0/23 (0%)		1/23 (4.3%)
Injury, poisoning and procedural complications
Thermal Burn	1/23 (4.3%)		0/23 (0%)
Investigations
Hemoglobin Decreased	0/23 (0%)		1/23 (4.3%)
Neutrophil Count Decreased	0/23 (0%)		1/23 (4.3%)
Weight Decreased	1/23 (4.3%)		0/23 (0%)
Metabolism and nutrition disorders
Anorexia	1/23 (4.3%)		2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain	1/23 (4.3%)		1/23 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Liver	1/23 (4.3%)		0/23 (0%)
Nervous system disorders
Neuropathy Peripheral	1/23 (4.3%)		2/23 (8.7%)
Headache	1/23 (4.3%)		0/23 (0%)
Memory Impairment	1/23 (4.3%)		0/23 (0%)
Migraine	0/23 (0%)		1/23 (4.3%)
Hypoaesthesia	0/23 (0%)		1/23 (4.3%)
Psychiatric disorders
Confusional State	1/23 (4.3%)		0/23 (0%)
Renal and urinary disorders
Hematuria	1/23 (4.3%)		0/23 (0%)
Proteinuria	1/23 (4.3%)		0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	3/23 (13%)		2/23 (8.7%)
Dyspnea	0/23 (0%)		2/23 (8.7%)
Hemoptysis	0/23 (0%)		1/23 (4.3%)
Cough	0/23 (0%)		1/23 (4.3%)
Rhinorrhoea	1/23 (4.3%)		0/23 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/23 (0%)		1/23 (4.3%)
Palmar-Plantar Erythrodysasthesia Syndrome	0/23 (0%)		1/23 (4.3%)
Alopecia	1/23 (4.3%)		1/23 (4.3%)
Rash	1/23 (4.3%)		1/23 (4.3%)
Pruritus	0/23 (0%)		1/23 (4.3%)
Vascular disorders
Hypertension	2/23 (8.7%)		2/23 (8.7%)

Limitations/Caveats

Based on the early safety results from this study, further recruitment and treatment was halted. Insufficient efficacy data were available to perform all protocol-specified analyses and limited the interpretation of the analyses performed.

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Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study.