Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy
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|ClinicalTrials.gov Identifier: NCT00225758|
Recruitment Status : Terminated (slow accrual)
First Posted : September 26, 2005
Results First Posted : July 27, 2018
Last Update Posted : July 27, 2018
Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present.
Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis. Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined.
Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Lapatinib||Phase 2|
All patients must have stopped their endocrine two to four weeks or longer prior to entry on study. Upon enrollment, patients will begin lapatinib at 1500 mg once a day orally. The original endocrine therapy will resume two weeks later. The lapatinib will be continued for a maximum of 26 weeks.
A history, physical examination, blood counts, and chemistries will be done at baseline, and at regular intervals through the course of the study. A CT scan and bone scan will be done prior to treatment and at weeks 14 and 26. Assays for plasma DNA will be performed on blood sampled at baseline and at multiple time points throughout the course of treatment. Percutaneous biopsies will be taken in selected patients with accessible disease, 72 hours or less prior to the start of lapatinib, and again 13-15 days, and 27-29 days following the start of lapatinib. The day 13-15 biopsy will be done just prior to the resumption of the patient's endocrine therapy. Assays for phospho-ERK, phospho-Akt, Cyclin D1, Ki-67, and IRS-1 will be performed by conventional immunohistochemistry on the biopsied tissue.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Lapatinib in Endocrine-Resistant Metastatic Breast Cancer|
|Study Start Date :||January 2006|
|Actual Primary Completion Date :||October 2011|
|Actual Study Completion Date :||October 2011|
Subjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer.
1500 mg po daily for 26 weeks or longer
Other Name: Tykerb
- Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib. [ Time Frame: 26 weeks ]A response is defined as stable disease or better at 26 weeks. Twenty two patients are evaluable for response
- Progression-free Survival [ Time Frame: Up to 575 days ]Progression-free survival is the time between date on study and progression based on RECIST criteria.
- Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer [ Time Frame: 26 weeks ]
- Determine Changes in Activation of Tumor Cell ERK and Akt, as Between the Hormonal Agent and Lapatinib Contributes to the Molecular Pharmacodynamic Effect Postulated Above. [ Time Frame: 4 weeks ]
- Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib [ Time Frame: 14 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00225758
|United States, Colorado|
|University of Colorado Cancer Center|
|Aurora, Colorado, United States, 80045|
|United States, New Hampshire|
|Norris Cotton Cancer Center|
|Lebanon, New Hampshire, United States, 03756|
|United States, New York|
|North Shore University Hospital|
|Lake Success, New York, United States, 11042|
|Principal Investigator:||Gary N Schwartz, MD||Norris Cotton Cancer Center|