Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute GlaxoSmithKline
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00470704

Purpose

In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: Lapatinib Drug: Herceptin	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Trastuzumab Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2 Study of Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer

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

Primary Outcome Measures:

To evaluate the rate of objective response by RECIST to combination therapy with lapatinib and trastuzumab, in the first-line and second/third line settings. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate further the safety and toxicity of combined lapatinib plus trastuzumab [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
To describe time to progression, site(s) of first progression, clinical benefit rate, and overall survival in patients treated with combined lapatinib plus trastuzumab. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	85
Study Start Date:	May 2007
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Oral dose taken daily

Given intravenously once a week

Detailed Description:

Participants will be asked to undergo a biopsy of an area of the body where the cancer has spread.
Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time you will be taking lapatinib, once per day.
Participants will receive Herceptin once every week through a vein.
During all treatment cycles a physical exam will be performed and questions about the participants general health will be asked. Blood tests including chemistry and hematology will be performed to measure additional effect of the study drug and disease status. Photographs may be taken of the tumor to assess the response of the tumor to treatment.
A PET/CT scan will be performed one week after the first dose of lapatinib. CT scans will be repeated every 8 weeks to assess the effect of the study treatment on the cancer. Either a MUGA scan or echocardiogram will be performed 8 weeks and 16 weeks after the participant starts the study treatment.
Participants will remain on this research study for as long as they are benefiting from the study treatment.

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 stage IV disease
HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
Willingness to undergo a research biopsy of recurrent or metastatic disease
Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
Completed radiation therapy at least 7 days prior to beginning protocol treatment
Cohort 1: No prior chemotherapy for advanced breast cancer; no prior trastuzumab in the advanced breast cancer setting; nor prior treatment with lapatinib or other HER2-directed therapy other than trastuzumab
Cohort 2: Up to two prior chemotherapy regimens for the treatment of advanced breast cancer; no prior treatment with lapatinib or other HER2-directed therapy except for trastuzumab
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 protocol
Cardiac ejection fraction, as assessed by either MUGA scan or echocardiogram greater than or equal to 50%
Able to take oral medications

Exclusion Criteria:

Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
Active brain metastases
History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
Clinically significant malabsorption syndrome
Uncontrolled intercurrent illness
Pregnant or breastfeeding women
Concurrent use of the medications listed in the protocol because of possible interaction with lapatinib

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470704

Contacts

Contact: Nancy Lin, MD	617-632-3800	nlin@partners.org
Contact: Kathryn Josephs	617-582-7652	kjosephs@partners.org

Locations

United States, Alabama
University fo Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35294
Contact: Carla Falkson, MD 205-975-2691
Contact: Pam Dixon, RN 205-975-5387 pam.dixon@ccc.uab.edu
Principal Investigator: Carla Falkson, MD
United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60452
Contact: Rita Nanda, MD 773-834-2756 rnanda@medicine.bsd.uchicago.edu
Contact: Eziamaka Okafar 773-702-3936 eokafor@bsd.uchicago.edu
Principal Investigator: Rita Nanda, MD
United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nancy Lin, MD 617-632-3800 nlin@partners.org
Contact: Katie Josephs 617-582-7652 kjosephs@partner.org
Principal Investigator: Nancy Lin, MD
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Steven Come, MD 617-667-4599
Principal Investigator: Steve Come, MD
Dana-Farber at Faulkner Hospital	Recruiting
Boston, Massachusetts, United States, 02130
Contact: Nancy Lin, MD 617-632-3800 nlin@partners.org
Principal Investigator: Nancy Lin, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Timothy Hobday, MD 507-285-3784 hobday.timothy@mayo.edu
Contact: Jacquelyn Chonis 507-284-1887 chonis.jacquelyn@mayo.edu
Principal Investigator: Timothy Hobday, MD
United States, North Carolina
University of North Carolina	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Claire Dees, MD 919-843-7714 claire_dees@med.unc.edu
Contact: Maureen Beeler, RN 919-966-4432 maureen_beeler@med.unc.edu
Principal Investigator: Claire Dees, MD
United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Ingrid Mayer, MD 615-936-2033
Contact: Teresa Foster, RN 615-936-1164 teresa.foster@vanderbilt.edu
Principal Investigator: Ingrid Mayer, MD
United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Mothaffar Rimawi, MD 713-798-1999 rimawi@bcm.edu
Contact: Claudette Foreman 713-798-7315 caforema@bcm.tmc.edu
Principal Investigator: Mothaffar Rimawi, MD

Sponsors and Collaborators

Dana-Farber Cancer Institute

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:	06-213
Study First Received:	May 7, 2007
Last Updated:	January 26, 2009
ClinicalTrials.gov Identifier:	NCT00470704 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

HER2-positive breast cancer
Herceptin
trastuzumab

Study placed in the following topic categories:

Skin Diseases
Trastuzumab
Breast Neoplasms

Lapatinib
Protein Kinase Inhibitors
Breast Diseases

Additional relevant MeSH terms:

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

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Trastuzumab
Breast Diseases

ClinicalTrials.gov processed this record on May 07, 2009