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Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00225758
Recruitment Status : Terminated (slow accrual)
First Posted : September 26, 2005
Results First Posted : July 27, 2018
Last Update Posted : July 27, 2018
University of Colorado, Denver
North Shore University Hospital
Information provided by (Responsible Party):
Gary Schwartz, Dartmouth-Hitchcock Medical Center

Brief Summary:

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Subjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer.
Drug: Lapatinib
1500 mg po daily for 26 weeks or longer
Other Name: Tykerb

Primary Outcome Measures :
  1. 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

  2. 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.

Secondary Outcome Measures :
  1. Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer [ Time Frame: 26 weeks ]
  2. 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 ]
  3. Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib [ Time Frame: 14 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with histologically or cytologically proven metastatic breast cancer.
  • Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.
  • Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.
  • Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.
  • Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.
  • Patients must have stopped fulvestrant at least four weeks prior and other endocrine therapy at least two weeks prior to enrollment on study.
  • Patients must have either measurable disease or at least one evaluable bone lesion that has not been irradiated. Measurable disease is not necessary.
  • Estimated life expectancy of at least 6 months.
  • ECOG performance status 0-2.
  • Adequate hematologic, hepatic, and renal function.
  • Patients must be post-menopausal, or they must be practicing either abstinence or an adequate method of contraception, or their sexual partner must be sterile.
  • All patients must be able to swallow, retain, and absorb oral medications.
  • All patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.

Exclusion Criteria:

  • Patients may not have received an investigational agent within the prior four weeks.
  • Patients may not have received trastuzumab within three weeks of study entry.
  • Patients may not have had major surgery within the prior two weeks.
  • Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.
  • Patients may not have a left ventricular ejection fraction < 40% based on MUGA or echocardiogram.
  • Patients may not have uncontrolled brain metastases or leptomeningeal disease.
  • Patients may not have rapidly progressive visceral metastases.
  • Patients may not have a serious illness or conditions including clinically significant cardiac disease, angina pectoris, serious psychiatric disorder, or an active infection.
  • Patients may not be receiving concurrent medications (listed in the protocol) which may interact with lapatinib during treatment with lapatinib.

Information from the National Library of Medicine

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 identifier (NCT number): NCT00225758

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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
Sponsors and Collaborators
Gary Schwartz
University of Colorado, Denver
North Shore University Hospital
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Principal Investigator: Gary N Schwartz, MD Norris Cotton Cancer Center
Additional Information:
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Responsible Party: Gary Schwartz, Staff Physician, Dartmouth-Hitchcock Medical Center Identifier: NCT00225758    
Other Study ID Numbers: D-0520
First Posted: September 26, 2005    Key Record Dates
Results First Posted: July 27, 2018
Last Update Posted: July 27, 2018
Last Verified: July 2018
Keywords provided by Gary Schwartz, Dartmouth-Hitchcock Medical Center:
breast cancer
endocrine therapy
drug resistance
epidermal growth factor receptor
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action