Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Letrozole
Intervention description: Treatment is intermittent with possible breaks between each 28 day treatment cycle if CA 15-3 or CA 27.29 level that has decreased by at least 50% of that individual patient's baseline or peak level on firstline letrozole or anastrozole therapy or has decreased into the normal reference range per institutional parameters. Letrozole or anastrozole therapy will be interrupted until CA 15-3 or CA 27.29 levels rise by at least 25% above trough CA 15-3 or CA 27.29 level. If the trough level is in the normal reference range then the CA 15-3 or CA 27.29 must rise into the normal reference range.
Intervention MeSH terms: Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: aromatase inhibitor; CA 15-3; Hormone receptor positive

Summary:

      The purpose of this research study is to study the effects of using aromatase inhibitor (AI)
      therapy intermittently on participants with breast cancer. AIs are a class of drugs used to
      treat breast cancer in postmenopausal women. They work by decreasing the level of estrogen,
      which is believed to stimulate the growth of tumor tissue. Breast cancer that progresses
      despite therapy with an AI is thought to have become resistant to AI therapy. There is
      scientific evidence to suggest that resistant breast cancer cells learn to grow at the very
      low levels of estrogen present on AI therapy, and that increasing estrogen levels even
      slightly by stopping AI therapy may inhibit the breast cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female

          -  18 years of age or older

          -  Postmenopausal

          -  Histologically or cytologically confirmed adenocarcinoma of the breast with locally
             advanced or metastatic disease this is not considered amenable to curative treatment
             with elevation of CA 15-3 documented at the time of diagnosis of metastatic disease
             and prior to initiation of letrozole or anastrozole therapy

          -  Current letrozole or anastrozole monotherapy with a documented CA 15-3 level that has
             decreased by at least 50% of the patients baseline

          -  Letrozole or anastrozole must be discontinued at the time of study enrollment

          -  Evidence of hormone sensitivity of primary or secondary tissue.

          -  Measurable or nonmeasurable (but evaluable-defined as nontarget lesions) disease
             according to modified RECIST

          -  Prior antiestrogen therapies including tamoxifen, steroidal AIs, nonsteroidal AIs, or
             fulvestrant in the adjuvant setting is allowed provided the patient is currently on
             letrozole or anastrozole monotherapy as first-line therapy for metastatic disease

          -  Life expectancy of greater than 3 months

          -  ECOG (Eastern Cooperative Oncology Group) Performance Status of 0,1, or 2

          -  Normal organ and marrow function as outlined in protocol

        Exclusion Criteria:

          -  Premenopausal

          -  Trastuzumab or biologic therapy within 2 weeks

          -  Prior or planned radiation therapy to a site of evaluable disease in the event that
             the site is the only site of evaluable disease

          -  Concomitant anticancer treatments including trastuzumab, chemotherapy, or other
             biologic agents other than letrozole or anastrozole therapy

          -  Chronic bisphosphonates for hypercalcemia or prevention of bone metastases.

          -  Treatment with non-approved or investigational agent within 2 weeks before study entry

          -  Presence of life-threatening metastatic disease, defined as extensive hepatic
             involvement, or past or present brain or leptomeningeal involvement, or symptomatic
             pulmonary lymphangitic spread

          -  Patients who are highly symptomatic from their breast cancer, or who require urgent
             palliative chemotherapy, as decided by their treating physician

          -  Previous or current systemic malignancy within the past five years, except for
             contralateral breast carcinoma, in situ carcinoma of the cervix treated by cone
             biopsy, or adequately treated basal or squamous cell carcinoma of the skin.

          -  Any severe concomitant condition believed to render subject undesirable for
             participation