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

NCT ID: NCT00470704

Last Updated: 2024-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-14
• Study Completion Date: 2024-08-20

Brief Summary

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.

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 or once every 3 weeks 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.
• 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.

Conditions

Breast Cancer

Keywords

HER2-positive breast cancer; Herceptin; trastuzumab

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

This cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year.

1000 mg daily Lapatinib

2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab

Group Type: OTHER

Lapatinib

Intervention Type: DRUG

Herceptin

Intervention Type: DRUG

Cohort 2

This cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy

1000 mg daily Lapatinib

2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab

Group Type: OTHER

Lapatinib

Intervention Type: DRUG

Herceptin

Intervention Type: DRUG

Interventions

Lapatinib

Intervention Type: DRUG

Herceptin

Intervention Type: DRUG

Other Intervention Names

Tykerb; trastuzumab

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Nancy Lin, MD

OTHER

Sponsor Role: lead

Responsible Party

Nancy Lin, MD

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nancy Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University fo Alabama at Birmingham

Birmingham, Alabama, United States

University of Chicago

Chicago, Illinois, United States

Dana-Farber at Faulkner Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003). J Clin Oncol. 2015 Aug 20;33(24):2623-31. doi: 10.1200/JCO.2014.60.0353. Epub 2015 Jul 13.

Reference Type: DERIVED

PMID: 26169615 (View on PubMed)

Other Identifiers

06-213

Identifier Type: -

Identifier Source: org_study_id