Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Nancy Lin, MD
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: September 11, 2012
Last verified: September 2012
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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 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized 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:
- 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: | December 2012 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Lapatinib
Orally twice daily
Procedure: Whole Brain Radiation
15 treatments over a period of 3 weeks
- 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
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 |
| Last Updated: | September 11, 2012 |
| 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 Lapatinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013