Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

NCT01004172 | Completed Phase 2 Results DMC

• 1 other identifier: 09-224
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

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.

Conditions

Metastatic Breast Cancer; Breast Cancer; Progressive Breast Cancer

Keywords

carboplatin; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Central Nervous System (CNS) Objective Response Rate

  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

  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.

Secondary Outcomes (4)

• 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.

• 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.

• 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.

• Overall Survival

  Maximum survival follow-up for the study cohort was 66 months.

Study Arms (1)

carboplatin, bevacizumab, trastuzumab (if HER2+)

EXPERIMENTAL

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; Drug: herceptin

Interventions

carboplatin DRUG

carboplatin, bevacizumab, trastuzumab (if HER2+)

bevacizumab DRUG

Also known as: Avastin

carboplatin, bevacizumab, trastuzumab (if HER2+)

herceptin DRUG

Also known as: trastuzumab

carboplatin, bevacizumab, trastuzumab (if HER2+)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Leone JP, Emblem KE, Weitz M, Gelman RS, Schneider BP, Freedman RA, Younger J, Pinho MC, Sorensen AG, Gerstner ER, Harris G, Krop IE, Morganstern D, Sohl J, Hu J, Kasparian E, Winer EP, Lin NU. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Res. 2020 Nov 30;22(1):131. doi: 10.1186/s13058-020-01372-w.

  PMID: 33256829 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Bevacizumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nancy Lin, MD
• Organization: Dana-Farber Cancer Institure

nlin@partners.org

617.632.2335

Study Officials

• Nancy Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 28, 2009
• First Posted: October 29, 2009
• Study Start: November 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2017
• Last Updated: December 14, 2018
• Results First Posted: May 22, 2017

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)