Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01004172
• Collaborator: Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other), Beth Israel Deaconess Medical Center (Other), Genentech, Inc. (Industry)
• Enrollment: 38
• Locations: 3
• Arm: 1
• Actual Duration (Months): 87
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine how well the combination of bevacizumab and carboplatin works in treating breast cancer that has spread to the brain. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body) that is made in the laboratory. Bevacizumab works differently from the way chemotherapy drugs work. Usually chemotherapy drugs attack fast growing cancer cells in the body. Bevacizumab works to slow or stop the growth of cells in cancer tumors by decreasing the blood supply to the tumors. When the blood supply is decreased, the tumors don't get the oxygen and nutrients they need to grow. Carboplatin is in a class of drugs known as platinum-containing compounds and has been approved for use in the treatment of ovarian cancer. Information from other research studies suggests that the combination of bevacizumab with carboplatin may be effective in treating breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Breast Cancer; Progressive Breast Cancer	Drug: carboplatin; Drug: bevacizumab; Drug: herceptin	Phase 2

Detailed Description

This study used a two-stage design to evaluate efficacy bevacizumab and carboplatin based on Central Nervous System (CNS) response. The null and alternative therapy response rates are 5% versus 20%. If 1 or more participants assessable in the stage one cohort (n=12 assessable participants) achieve CNS response then accrual proceeds to stage two (n=25 additional assessable participants). If at least 4 participants in the final set of 37 assessable participants achieve CNS response then this regimen would be deemed worthy of further study. The probability of stopping early is 0.54 if the true CNS response rate is 5% and 0.07 if the true CNS response rate is 20%. The probability of deeming the treatment worthy of further study is 0.10 and 0.90 if the true CNS response rate is 5% and 20%, respectively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases
• Actual Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: carboplatin, bevacizumab, trastuzumab (if HER2+) Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2

Drug: carboplatin; Drug: bevacizumab; Other Names: Avastin ; Drug: herceptin; Other Names: trastuzumab

Outcome Measures

Primary Outcome Measures

1. Central Nervous System (CNS) Objective Response Rate [Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.]

   CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows: CNS complete response (CR) is achieved if all of the following are satisfied: Complete resolution of all measurable (>= 1 cm in longest dimension [LD]) and non-measurable brain metastases No new CNS lesions (defined as any new lesion >= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST CNS partial response (PR) is achieved if all of the following are satisfied: ->/= 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline No progression on non-measurable lesions No new CNS lesions (defined as any new lesion >/= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST

Secondary Outcome Measures

1. Progression-Free Survival [Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.]

   Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression (PD), second cancer, or death, whichever occurs first. PD if any of the following occur: CNS Disease >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment Progression of non-measurable lesions New lesions (>/=6 mm) Non-CNS Disease • RECIST 1.0 criteria: at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded on treatment or the appearance of >/=1 new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Symptomatic Increasing steroid requirement Global deterioration of health status requiring discontinuation of treatment New/progression tumor-related neurologic signs and symptoms except for transient worsening lasting </=14 days

2. CNS Best Response [Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.]

   CNS best response was defined based on standard criteria. Adding to CR and PR (defined in the primary outcome measure): CNS stable disease (SD) is achieving all the following: < 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline No progression on non-measurable lesions No new CNS lesions (defined as any new lesion >/= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST CNS Progressive Disease (PD) was experiencing any of the following: ->/- 40% increase in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline Progression on non-measurable lesions New CNS lesions (defined as any new lesion >/= 6 mm in LD) Increasing steroid dose New/progressive tumor-related neurologic signs or symptoms Progression of extra-CNS disease as assessed by RECIST

3. Site of First Progression [Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.]

   Site of first progression is classified as follows: CNS Disease >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment Progression of non-measurable lesions New lesions (>/=6 mm) Non-CNS Disease Per RECIST 1.0 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Symptomatic Increasing steroid requirement Global deterioration of health status requiring discontinuation of treatment New/progression tumor-related neurologic signs and symptoms (NSS) except for transient worsening lasting </=14 days

4. Overall Survival [Maximum survival follow-up for the study cohort was 66 months.]

   Participants were assessed every 6 months post-treatment. Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast cancer, with metastatic disease. patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study

• Measurable disease. Patients must have measurable CNS disease, defined as at least one parenchymal brain lesion that can be accurately measured in at least one dimension with longest dimension >/= 10mm by local radiology review

• New or progressive CNS lesions, as assessed by the patient's treating physician

• No increase in corticosteroid dose in the week prior to the baseline brain MRI

• 18 years of age or older

• Life expectancy of greater than 12 weeks

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

• Normal organ and marrow function as outlined in the protocol

• Left ventricular ejection fraction >/= 50%, as determined by radionuclide ventriculography (RVG) or echocardiogram within 60 days prior to initiation of protocol therapy

• Prior carboplatin is allowed if it was not given in conjunction with bevacizumab

• Prior trastuzumab is allowed

• No prior bevacizumab since diagnosis of CNS metastases or within 6 months prior to diagnosis of CNS metastases

• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Patients who have had chemotherapy within 14 days prior to entering the study, or those who have not recovered adequately from adverse events due to agents administered earlier

• Patients may not receive any concurrent investigational agents while on study

• Patients may not receive any cancer-directed concurrent therapy , such as concurrent chemotherapy, radiotherapy, or hormonal therapy while on study. Concurrent treatment with bisphosphonates is allowed

• History of Grade 3 or 4 allergic reactions attributed to compounds of similar or identical biologic composition to bevacizumab, carboplatin, or trastuzumab

• Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker, shrapnel, or ocular foreign body

• Leptomeningeal carcinomatosis as the only site of CNS involvement

• More than 2 seizures over last 4 weeks prior to study entry

• Grade 1 or higher CNS hemorrhage on baseline brain MRI

• History of grade 2 or higher CNS hemorrhage within 12 months of study entry

• Inadequately controlled hypertension

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infraction or unstable angina within 6 months prior to day 1

• Significant vascular disease within 6 months prior to day 1

• History of hemoptysis within 1 month prior to day 1

• Evidence of bleeding diathesis or significant coagulopathy

• Current, ongoing treatment with full-dose warfarin or its equivalent

• Use of aspirin (>325 mg/day) within 10 days prior to day 1

• 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 as demonstrated by a urine protein-creatinine ratio >/= 1.0 at screening

• Known hypersensitivity to any component of bevacizumab

• Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• Massachusetts General Hospital
• Beth Israel Deaconess Medical Center
• Genentech, Inc.

Investigators

• Principal Investigator: Nancy Lin, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nancy Lin, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01004172
• Other Study ID Numbers: 09-224
• First Posted: Oct 29, 2009
• Last Update Posted: Dec 14, 2018
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Nancy Lin, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute: carboplatin; bevacizumab
• Additional relevant MeSH terms: Breast Neoplasms; Brain Neoplasms; Bevacizumab; Trastuzumab; Carboplatin

Study Results

Participant Flow

Recruitment Details	Participants were recruited between November 2009 and August 2012.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Period Title: Overall Study
STARTED	38
COMPLETED	0
NOT COMPLETED	38

Baseline Characteristics

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Overall Participants	38
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	38 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.6%
Not Hispanic or Latino	37 97.4%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	34 89.5%
Black or African-American	1 2.6%
Asian	3 7.9%
Region of Enrollment (participants) [Number]
United States	38 100%

Outcome Measures

1. Primary Outcome

Title	Central Nervous System (CNS) Objective Response Rate
Description	CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows: CNS complete response (CR) is achieved if all of the following are satisfied: Complete resolution of all measurable (>= 1 cm in longest dimension [LD]) and non-measurable brain metastases No new CNS lesions (defined as any new lesion >= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST CNS partial response (PR) is achieved if all of the following are satisfied: ->/= 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline No progression on non-measurable lesions No new CNS lesions (defined as any new lesion >/= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST
Time Frame	Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of assessable participants. Per protocol, assessable is defined as those who have at least one lesion on baseline MRI with longest with longest diameter >10 mm on T1-weighted, gadolinium-enhanced. All enrolled participants were assessable.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	63 165.8%

2. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression (PD), second cancer, or death, whichever occurs first. PD if any of the following occur: CNS Disease >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment Progression of non-measurable lesions New lesions (>/=6 mm) Non-CNS Disease • RECIST 1.0 criteria: at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded on treatment or the appearance of >/=1 new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Symptomatic Increasing steroid requirement Global deterioration of health status requiring discontinuation of treatment New/progression tumor-related neurologic signs and symptoms except for transient worsening lasting </=14 days
Time Frame	Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 HER-2: human epidermal growth factor receptor 2
Measure Participants	38
Median (95% Confidence Interval) [months]	5.6

3. Secondary Outcome

Title	CNS Best Response
Description	CNS best response was defined based on standard criteria. Adding to CR and PR (defined in the primary outcome measure): CNS stable disease (SD) is achieving all the following: < 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline No progression on non-measurable lesions No new CNS lesions (defined as any new lesion >/= 6 mm in LD) Stable or decreasing steroid dose No new/progressive tumor-related neurologic signs or symptoms No progression of extra-CNS disease as assessed by RECIST CNS Progressive Disease (PD) was experiencing any of the following: ->/- 40% increase in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline Progression on non-measurable lesions New CNS lesions (defined as any new lesion >/= 6 mm in LD) Increasing steroid dose New/progressive tumor-related neurologic signs or symptoms Progression of extra-CNS disease as assessed by RECIST
Time Frame	Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of assessable participants. Per protocol, assessable is defined as those who have at least one lesion on baseline MRI with longest with longest diameter >10 mm on T1-weighted, gadolinium-enhanced. All enrolled participants were assessable.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
Measure Participants	38
Complete Response	0 0%
Partial Response	24 63.2%
Stable Disease >/=24 weeks	2 5.3%
Stable Disease < 24 weeks	5 13.2%
Progressive Disease	7 18.4%

4. Secondary Outcome

Title	Site of First Progression
Description	Site of first progression is classified as follows: CNS Disease >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment Progression of non-measurable lesions New lesions (>/=6 mm) Non-CNS Disease Per RECIST 1.0 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Symptomatic Increasing steroid requirement Global deterioration of health status requiring discontinuation of treatment New/progression tumor-related neurologic signs and symptoms (NSS) except for transient worsening lasting </=14 days
Time Frame	Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled participants.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 HER-2: human epidermal growth factor receptor 2
Measure Participants	38
CNS	15 39.5%
Non-CNS	12 31.6%
Both CNS and Non-CNS	6 15.8%
Symptomatic	2 5.3%
No Site	3 7.9%

5. Secondary Outcome

Title	Overall Survival
Description	Participants were assessed every 6 months post-treatment. Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Time Frame	Maximum survival follow-up for the study cohort was 66 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of enrolled patients.

Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 HER-2: human epidermal growth factor receptor 2
Measure Participants	38
Median (95% Confidence Interval) [months]	14

Adverse Events

Time Frame	Adverse events (AEs) were assessed day 1 of each cycle throughout the treatment period. Median (range) treatment duration for this study cohort was 8 cycles (1-20) which approximates months given the 4-week cycle duration.
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3). All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
Arm/Group Description	Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2
All Cause Mortality
	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Serious Adverse Events
	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
	Affected / at Risk (%)	# Events
Total	16/38 (42.1%)
Blood and lymphatic system disorders
Hemoglobin	1/38 (2.6%)
Eye disorders
Ocular-other	1/38 (2.6%)
General disorders
Fatigue	6/38 (15.8%)
Investigations
Leukocytes	1/38 (2.6%)
Neutrophils	3/38 (7.9%)
Platelets	4/38 (10.5%)
ALT, SGPT	1/38 (2.6%)
AST, SGOT	2/38 (5.3%)
Metabolism and nutrition disorders
Hypercalcemia	1/38 (2.6%)
Hyponatremia	1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/38 (2.6%)
Joint, pain	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing	1/38 (2.6%)
Vascular disorders
Hypertension	1/38 (2.6%)
Thrombosis/thrombus/embolism	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Carboplatin, Bevacizumab, Trastuzumab (if HER2+)
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	2/38 (5.3%)
Hemoglobin	2/38 (5.3%)
Hemoglobin	29/38 (76.3%)
Cardiac disorders
Cardiac-other	1/38 (2.6%)
Left ventricular systolic dysfunction	5/38 (13.2%)
Palpitations	1/38 (2.6%)
Endocrine disorders
Cushingnoid appearance	1/38 (2.6%)
Eye disorders
Double vision	1/38 (2.6%)
Neuropathy CN II vision	1/38 (2.6%)
Ocular-other	2/38 (5.3%)
Tearing	1/38 (2.6%)
Vision-blurred	2/38 (5.3%)
Gastrointestinal disorders
Abdomen, hemorrhage NOS	2/38 (5.3%)
Abdomen, pain	3/38 (7.9%)
Colon, hemorrhage	3/38 (7.9%)
Constipation	2/38 (5.3%)
Constipation	14/38 (36.8%)
Dental/teeth/peridontal, pain	1/38 (2.6%)
Diarrhea w/o prior colostomy	2/38 (5.3%)
Diarrhea w/o prior colostomy	11/38 (28.9%)
Dyspepsia	2/38 (5.3%)
Esophagitis	1/38 (2.6%)
Flatulence	1/38 (2.6%)
GI-other	4/38 (10.5%)
Jejunum, hemorrhage	1/38 (2.6%)
Muco/stomatitis (symptom) oral cavity	1/38 (2.6%)
Muco/stomatitis by exam, oral cavity	1/38 (2.6%)
Nausea	2/38 (5.3%)
Nausea	17/38 (44.7%)
Oral cavity, hemorrhage	1/38 (2.6%)
Rectum, hemorrhage	6/38 (15.8%)
Stomach, pain	1/38 (2.6%)
Vomiting	2/38 (5.3%)
Vomiting	6/38 (15.8%)
General disorders
Chest/thoracic pain NOS	1/38 (2.6%)
Constitutional, other	5/38 (13.2%)
Edema head and neck	1/38 (2.6%)
Extremity-lower (gait/walking)	1/38 (2.6%)
Fatigue	4/38 (10.5%)
Fatigue	27/38 (71.1%)
Fever w/o neutropenia	2/38 (5.3%)
Pain-other	5/38 (13.2%)
Rigors/chills	1/38 (2.6%)
Immune system disorders
Allergic reaction	3/38 (7.9%)
Allergic reaction	5/38 (13.2%)
Infections and infestations
Infection Gr0-2 neut, dental-tooth	1/38 (2.6%)
Infection Gr0-2 neut, sinus	3/38 (7.9%)
Infection Gr0-2 neut, upper airway	4/38 (10.5%)
Infection Gr0-2 neut, upper airway	1/38 (2.6%)
Infection Gr0-2 neut, urinary tract	1/38 (2.6%)
Infection w/ unk ANC sinus	1/38 (2.6%)
Infection-other	1/38 (2.6%)
Injury, poisoning and procedural complications
Bruising	2/38 (5.3%)
Investigations
Alkaline phosphatase	13/38 (34.2%)
ALT, SGPT	14/38 (36.8%)
AST, SGOT	23/38 (60.5%)
Creatinine	2/38 (5.3%)
Creatinine	4/38 (10.5%)
Hypercholesterolemia	2/38 (5.3%)
INR	1/38 (2.6%)
Leukocytes	20/38 (52.6%)
Lymphopenia	2/38 (5.3%)
Metabolic/Laboratory-other	4/38 (10.5%)
Neutrophils	4/38 (10.5%)
Neutrophils	20/38 (52.6%)
Platelets	3/38 (7.9%)
Platelets	27/38 (71.1%)
PTT	1/38 (2.6%)
Metabolism and nutrition disorders
Anorexia	8/38 (21.1%)
Dehydration	3/38 (7.9%)
Hypercalcemia	2/38 (5.3%)
Hyperglycemia	18/38 (47.4%)
Hypernatremia	1/38 (2.6%)
Hypoalbuminemia	2/38 (5.3%)
Hypocalcemia	5/38 (13.2%)
Hypoglycemia	1/38 (2.6%)
Hypokalemia	2/38 (5.3%)
Hypokalemia	4/38 (10.5%)
Hypomagnesemia	3/38 (7.9%)
Hyponatremia	6/38 (15.8%)
Musculoskeletal and connective tissue disorders
Back, pain	6/38 (15.8%)
Bone, pain	6/38 (15.8%)
Buttock, pain	1/38 (2.6%)
Chest wall, pain	1/38 (2.6%)
Extremity-limb, pain	7/38 (18.4%)
Joint, pain	6/38 (15.8%)
Musculoskeletal/soft tissue-other	3/38 (7.9%)
Neck, pain	1/38 (2.6%)
Nonneuropathic generalized weakness	1/38 (2.6%)
Nonneuropathic lower extr muscle weak	1/38 (2.6%)
Nonneuropathic right-side muscle weak	1/38 (2.6%)
Nervous system disorders
Ataxia	3/38 (7.9%)
Brachial plexopathy	1/38 (2.6%)
CNS cerebrovascular ischemia	2/38 (5.3%)
CNS, hemorrhage	2/38 (5.3%)
CNS, hemorrhage	4/38 (10.5%)
Cognitive disturbance	1/38 (2.6%)
Dizziness	7/38 (18.4%)
Head/headache	2/38 (5.3%)
Head/headache	20/38 (52.6%)
Hydrocephalus	1/38 (2.6%)
Laryngeal nerve dysfunction	1/38 (2.6%)
Memory impairment	2/38 (5.3%)
Mental status	2/38 (5.3%)
Neurologic-other	1/38 (2.6%)
Neuropathy-motor	2/38 (5.3%)
Neuropathy-sensory	2/38 (5.3%)
Neuropathy-sensory	14/38 (36.8%)
Seizure	2/38 (5.3%)
Sinus, pain	1/38 (2.6%)
Speech impairment	1/38 (2.6%)
Syncope	1/38 (2.6%)
Taste disturbance	2/38 (5.3%)
Tremor	1/38 (2.6%)
Psychiatric disorders
Anxiety	2/38 (5.3%)
Confusion	2/38 (5.3%)
Depression	2/38 (5.3%)
Insomnia	2/38 (5.3%)
Renal and urinary disorders
Cystitis	1/38 (2.6%)
Incontinence urinary	1/38 (2.6%)
Proteinuria	5/38 (13.2%)
Proteinuria	8/38 (21.1%)
Reproductive system and breast disorders
Breast, pain	2/38 (5.3%)
Vaginal dryness	2/38 (5.3%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/38 (7.9%)
Cough	10/38 (26.3%)
Dyspnea	3/38 (7.9%)
Larynx, pain	1/38 (2.6%)
Lung, hemorrhage	2/38 (5.3%)
Lung, hemorrhage	1/38 (2.6%)
Nasal cavity/paranasal sinus reaction	1/38 (2.6%)
Nose, hemorrhage	2/38 (5.3%)
Nose, hemorrhage	12/38 (31.6%)
Pneumothorax	1/38 (2.6%)
Pulmonary/Upper Respiratory-other	3/38 (7.9%)
Throat/pharynx/larynx, pain	4/38 (10.5%)
Voice changes/dysarthria	2/38 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	4/38 (10.5%)
Alopecia	5/38 (13.2%)
Dry skin	2/38 (5.3%)
Hand-foot reaction	3/38 (7.9%)
Nail changes	2/38 (5.3%)
Pruritus/itching	1/38 (2.6%)
Rash/desquamation	2/38 (5.3%)
Rash: acne/acneiform	1/38 (2.6%)
Scalp, pain	1/38 (2.6%)
Skin, pain	1/38 (2.6%)
Skin-other	4/38 (10.5%)
Sweating	1/38 (2.6%)
Ulceration	1/38 (2.6%)
Vascular disorders
Flushing	1/38 (2.6%)
Hot flashes	2/38 (5.3%)
Hypertension	3/38 (7.9%)
Hypertension	9/38 (23.7%)
Peripheral arterial ischemia	3/38 (7.9%)
Phlebitis	1/38 (2.6%)
Thrombosis/thrombus/embolism	3/38 (7.9%)
Visceral arterial ischemia	3/38 (7.9%)

Limitations/Caveats

[Not Specified]

More Information

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.