Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Nervous System Diseases

Neoplasm Metastasis

Breast Neoplasms

Brain Neoplasms

Breast Diseases

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Carboplatin

Bevacizumab

Mitogens

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

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

carboplatin

bevacizumab

herceptin

Nancy Lin, MD

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.

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.

Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

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

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

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

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

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.

Brigham and Women's Hospital

Massachusetts General Hospital

Beth Israel Deaconess Medical Center

Genentech, Inc.

Dana-Farber Cancer Institute

Assistant Professor of Medicine

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.

Carboplatin, Bevacizumab, Trastuzumab (if HER2+)

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African-American

Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

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.

Central Nervous System (CNS) Objective Response Rate

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases	NCT01004172	Metastatic Brea... Breast Cancer Progressive Bre...	carboplatin bevacizumab herceptin	18 Years -	Dana-Farber Cancer Institute
Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases	NCT01004172	Metastatic Brea... Breast Cancer Progressive Bre...	carboplatin bevacizumab herceptin	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for progressive breast cancer