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

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Breast Cancer Research Foundation
GlaxoSmithKline
Information provided by (Responsible Party):
Nancy Lin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00470847
First received: May 7, 2007
Last updated: April 28, 2014
Last verified: April 2014
  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
Drug: Herceptin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The Maximum Tolerated Dose of Lapatinib When Combined With Cranial Radiation in Patients With CNS Metastases From HER2-positive Breast Cancer. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose is defined as :The highest dose of a drug or treatment that does not cause unacceptable side effects.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Progression Free Survival is the time from date of start of treatment to the date of the first documented progression or death due to any cause. If a patient has not progressed or died, progression free survival is censored at the time of last tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20 % increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  • Objective Response Rate in Central Nervous System Sites [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Objective Response Rate was defined using volumetric response as the following: Complete Response (CR) is the disappearance of all target lesions, stable/responsive non-target lesions, and no new lesions. Partial response (PR) is at least a 50% reduction in the sum of the target lesions, stable/responsive non-target lesions, and no new lesions. Stable Disease (SD) is neither CR PR or Progressive Disease (PD). And Progressive Disease (PD) is at least 40% increase in sum of target lesionsor the appearance of any new lesion >=6mm in the longest dimension. If a patient progressed in a non-central nervous system(CNS) site first, died, or withdrew from the study for any reason after the first dose of drug was administered, and before a CR or PR in the central nervous system was determined, she was considered a CNS non-responder.

  • Percentage of Participants Having Central Nervous System as the Site of the First Progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Percentage of Participants Having Non-Central Nervous System Sites as the Site of First Progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Participants were followed for an average of 3.8 years ] [ Designated as safety issue: No ]
    Overall average length of participant survival after protocol initiation


Enrollment: 35
Study Start Date: April 2007
Study Completion Date: June 2012
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Lapatinib,Whole Brain Radiation,Herceptin
Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Drug: Lapatinib
Orally twice daily
Other Name: Tykerb
Procedure: Whole Brain Radiation
15 treatments over a period of 3 weeks
Drug: Herceptin
Herceptin 4mg/kg loading dose then 2 mg/kg IV once weekly, then once every three weeks after cycle 3.
Other Name: Trastuzumab

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
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: NCT00470847

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Nancy Lin, MD
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: Nancy Lin, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00470847     History of Changes
Other Study ID Numbers: 06-356
Study First Received: May 7, 2007
Results First Received: September 10, 2013
Last Updated: April 28, 2014
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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trastuzumab
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014