Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute Brigham and Women's Hospital Breast Cancer Research Foundation GlaxoSmithKline
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00470847

Purpose

The purpose of this research study is to determine the safety of combining lapatinib plus radiation in patients with breast cancer that has spread to the brain. Depending upon the participants cancer, they may also have stereotactic radiosurgery (SRS). Lapatinib s a compound that may stop cancer cells from growing abnormally. It is thought that lapatinib might also make cancer cells more sensitive to radiation. This drug has been used in other research studies in women with breast cancer, and information from those other research studies suggests that lapatinib may help to shrink or stabilize breast tumors both inside the brain and outside the brain.

Condition	Intervention	Phase
Breast Cancer Brain Metastases	Drug: Lapatinib Procedure: Whole Brain Radiation	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Radiation Therapy

Drug Information available for: Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	A Phase I Study of Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer

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

Primary Outcome Measures:

To determine the maximal tolerated dose and feasibility of lapatinib when combined with cranial radiation in patients with CNS metastases from HER2-positive breast cancer. [ Time Frame: Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To describe the time to progression, site of first progression, objective response in CNS and non-CNS sites, neurologic outcomes, quality of life, overall survival, and cause of death. [ Time Frame: years ] [ Designated as safety issue: No ]

Estimated Enrollment:	39
Study Start Date:	April 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Orally twice daily

15 treatments over a period of 3 weeks

Detailed Description:

Participant's will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks. On the first day of the treatment cycle, participants will take 1 lapatinib orally twice per day, 12 hours apart. After the first day, lapatinib will be taken once a day in the morning.
Whole brain radiation treatments will begin approximately 1-8 days after the first dose of lapatinib. The radiation treatments will follow standard guidelines and will be supervised by a radiation oncologist. Radiation will be given in 15 treatments over a period of three weeks.
Some participants will also undergo stereotactic radiosurgery (SRS). SRS is a highly focused and intense form of radiation treatment generally done as an outpatient procedure in a single treatment.
After whole brain radiation treatments are completed, lapatinib will be continued at the same dose for one more week. After that, the lapatinib dose may change. In addition at the same time, Herceptin will be started. Participants will continue with both lapatinib and herceptin together as long as there is evidence that they are benefitting from it.
During all treatment cycles participants will have a physical exam and be asked general questions about their health. Photographs will be taken of the tumor, if visible, to assess the response of the tumor to the treatment. An assessment of the tumor by CT scan of the body, and MRI imaging of the brain will be performed every two months. An assessment of heart function by MUGA scan or echocardiogram will be performed every 8 weeks. The participant will also be asked to complete a brief questionnaire measuring quality of life and asking about symptoms related to the cancer at baseline, 6 months, and one year. Blood tests will be performed every 4 weeks.

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
HER2 overexpressing breast cancer defined as 3+ staining by immunohistochemistry, or HER2 gene amplification by FISH
At least one parenchymal brain metastasis
Disease progression in the CNS as assessed by at least one of the following; new neurological signs or symptoms; new lesion(s) in the CNS on an imaging study; progressive lesions on an imaging study
At least two weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or major surgery for cancer
18 years of age or older
Life expectancy of greater than 12 weeks
ECOG performance status 0-2
Normal organ and marrow function as described in the protocol
Left ventricular ejection fraction > 50%
Able to swallow and retain oral medications

Exclusion Criteria:

Prior WBRT
Receiving any other investigational agents
Concurrent chemotherapy, immunotherapy, biologic therapy or hormonal therapy for treatment of their cancer
History of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to herceptin or lapatinib
Leptomeningeal carcinomatosis as the only site of CNS involvement
Concurrent treatment with medications that are either inducers of inhibitors of CYP3A4
Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or active ulcerative colitis
History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents
Other known contraindication to MRI
Uncontrolled intercurrent illness
History of other active malignancy except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
Pregnant or breastfeeding women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470847

Contacts

Contact: Nancy Lin, MD	617-632-5269	nlin@partners.org
Contact: Emily Eisenberg	617-632-6930	eeisenberg@partners.org

Locations

United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Anita Rush-Taylor, RN 317-278-6797 arushtay@iupui.edu
Principal Investigator: Anna Maria Storniolo, MD
United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Nancy Lin, MD
Sub-Investigator: Eric Winer, MD
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Naren Ramakrishna, MD

Sponsors and Collaborators

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Breast Cancer Research Foundation

GlaxoSmithKline

Investigators

Principal Investigator:

Nancy Lin, MD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( Nancy Lin, MD )
Study ID Numbers:	06-356
Study First Received:	May 7, 2007
Last Updated:	January 23, 2009
ClinicalTrials.gov Identifier:	NCT00470847 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

Herceptin
breast cancer
radiation therapy
stereotactic radiosurgery

SRS
whole brain radiation
WBRT

Study placed in the following topic categories:

Brain Neoplasms
Skin Diseases
Trastuzumab
Neoplasm Metastasis
Central Nervous System Diseases
Breast Neoplasms

Lapatinib
Central Nervous System Neoplasms
Brain Diseases
Protein Kinase Inhibitors
Nervous System Neoplasms
Breast Diseases

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Nervous System Diseases
Breast Neoplasms
Central Nervous System Diseases
Enzyme Inhibitors
Lapatinib
Central Nervous System Neoplasms
Brain Diseases
Protein Kinase Inhibitors

Pharmacologic Actions
Brain Neoplasms
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Neoplasm Metastasis
Breast Diseases
Nervous System Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009