Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Genentech, Inc.
Information provided by (Responsible Party):
Nancy Lin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01004172
First received: October 28, 2009
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Metastatic Breast Cancer
Breast Cancer
Progressive Breast Cancer
Drug: carboplatin
Drug: bevacizumab
Drug: herceptin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Central nervous system (CNS) objective response, defined as either complete response or partial response [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2009
Estimated Study Completion Date: February 2016
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
Carboplatin, trastuzumab (if HER2+), bevacizumab
Drug: carboplatin
Given intravenously on Day 8 of cycle one and Day 1 of each subsequent cycle.
Drug: bevacizumab
Given intravenously on day 1 of each cycle
Drug: herceptin
given intravenously for patients with HER2-positive breast cancer only

Detailed Description:
  • Participants will receive bevacizumab and carboplatin intravenously. In addition to bevacizumab and carboplatin, participants whose cancer is positive for HER2 will receive Herceptin intravenously. Herceptin is a standard treatment for patients with HER2-positive breast cancer.
  • The first treatment cycle lasts four weeks. Participants will receive bevacizumab on Day 1 and carboplatin on Day 8. After the first treatment cycle, each treatment cycle thereafter lasts three weeks and participants will receive bevacizumab and carboplatin together on Day 1 of each cycle.
  • Physical exams and vital signs will be performed and collected at multiple time points during the participants first treatment cycle and at the beginning of each cycle thereafter.
  • Participants will have a brain MRI and MRA between days 2-4 of the first treatment cycle and again at the end of the second treatment cycle for research purposes only. These scans are mandatory and must be performed at the Massachusetts General Hospital-Charlestown Navy Yard facility. A brain MRI will be performed every other cycle after that (the end of cycles 2, 4, 6, 8, etc.). Participants will also have CT or MRI scans of their body at the enof of every other treatment cycle.
  • MUGA or ECHO scans will be done every 4 treatment cycles.
  • Participants will have blood tests done on Day 8 of the first treatment cycle and at the beginning of every treatment cycle thereafter to check blood cell counts and how well their organs are functioning.
  • A urine test will be done every other cycle (at the beginning of cycles 3, 5, 7, etc.)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • ECOG performance status 0-2
  • Normal organ and marrow function as outlined in the protocol
  • Left ventricular ejection fraction >/= 50%, as determined by 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
  • 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 UPC ration >/= 1.0 at screening
  • Known hypersensitivity to any component of bevacizumab
  • Pregnancy or lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004172

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
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
  More Information

No publications provided

Responsible Party: Nancy Lin, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01004172     History of Changes
Other Study ID Numbers: 09-224
Study First Received: October 28, 2009
Last Updated: January 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
carboplatin
bevacizumab

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014