- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00470847
Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer
April 28, 2014 updated by: Nancy Lin, MD
A Phase I Study of Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Lapatinib,Whole Brain Radiation,Herceptin
Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
|
Orally twice daily
Other Names:
15 treatments over a period of 3 weeks
Herceptin 4mg/kg loading dose then 2 mg/kg IV once weekly, then once every three weeks after cycle 3.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
The maximum tolerated dose is defined as :The highest dose of a drug or treatment that does not cause unacceptable side effects.
|
5 Years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: 5 years
|
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.
|
5 years
|
Objective Response Rate in Central Nervous System Sites
Time Frame: 5 years
|
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.
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5 years
|
Percentage of Participants Having Central Nervous System as the Site of the First Progression
Time Frame: 5 years
|
5 years
|
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Percentage of Participants Having Non-Central Nervous System Sites as the Site of First Progression
Time Frame: 5 years
|
5 years
|
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Overall Survival
Time Frame: Participants were followed for an average of 3.8 years
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Overall average length of participant survival after protocol initiation
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Participants were followed for an average of 3.8 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2007
Primary Completion (Actual)
December 1, 2009
Study Completion (Actual)
June 1, 2012
Study Registration Dates
First Submitted
May 7, 2007
First Submitted That Met QC Criteria
May 7, 2007
First Posted (Estimate)
May 8, 2007
Study Record Updates
Last Update Posted (Estimate)
May 22, 2014
Last Update Submitted That Met QC Criteria
April 28, 2014
Last Verified
April 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Breast Neoplasms
- Neoplasm Metastasis
- Brain Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Trastuzumab
- Lapatinib
Other Study ID Numbers
- 06-356
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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