Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Lapatinib
Intervention description: 1500 mg po daily for 26 weeks or longer
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast cancer; endocrine therapy; drug resistance; lapatinib; epidermal growth factor receptor

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.
    

Eligibility criteria:

        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.