Randomized, Double Blind Multicenter Phase II Study of Time to Progression on Fulvestrant in Combination With Erlotinib or Placebo in Hormone Receptor-Positive Metastatic Breast Cancer (MBC) Subjects Who Progressed on First Line Hormonal Therapy
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fulvestrant; erlotinib; Fulvestrant; Placebo
Intervention description: Fulvestrant: 250 mg IM Q 4 weeks; 150 mg PO QD; 250 mg IM Q 4 weeks; Placebo 150 mg PO QD
Intervention MeSH terms: Erlotinib Hydrochloride; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This is a multicenter, randomized, double-blind study of fulvestrant plus erlotinib versus
      fulvestrant plus placebo for subjects with metastatic breast cancer whose disease progression
      after first line hormonal therapy.

        1. To obtain preliminary estimates of the magnitude and variability of the efficacy of
           fulvestrant in combination with erlotinib in this subject population, and

        2. To obtain historically up-to-date estimates of the magnitude and variability of the
           efficacy of fulvestrant as the sole active agent in this subject population.

      The measure of efficacy for both primary objectives will be time to progression.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must sign a written consent.

          2. Subjects must have estrogen- and/or progesterone-receptor-positive histologically
             confirmed adenocarcinoma of the breast with recurrent or metastatic carcinoma of the
             breast.

          3. Baseline measurements and evaluations of involved sites should be performed as close
             as possible to study entry, but must be within 4 weeks prior to randomization.

          4. Subjects fulfilling one of the following criteria are eligible to participate in the
             study: Subjects with measurable disease as per RECIST criteria. This is defined as at
             least one lesion that can be accurately measured in at least one dimension (longest
             diameter to be recorded) as over 20 mm with conventional technique or as over 10 mm
             with spiral CT scan or MRI. Subjects with bone lesions, lytic or mixed (lytic +
             sclerotic), in the absence of measurable disease as defined by RECIST criteria. The
             lytic component of at least one bone lesion should measure 20 mm with conventional
             techniques or 10 mm with spiral CT scan or MRI. At least one bone lesion satisfying
             these criteria must be outside any previously irradiated area.

          5. All subjects must be postmenopausal females defined by:

        Prior bilateral oophorectomy OR No menstrual period for 12 months or longer. If age 55
        years or less and on tamoxifen within the prior 6 months, must have an estradiol level in
        the postmenopausal range.

        Exclusion Criteria:

        1. Subjects must not have had more than 1 prior chemotherapy regimen for metastatic disease
        and no chemotherapy within 3 weeks prior to randomization. 2. No concurrent chemotherapy is
        allowed while on protocol therapy. Subjects whose adjuvant hormonal therapy was
        discontinued more than 12 months ago must have had only 1 prior hormonal therapy for
        metastatic disease. Subjects who relapsed while receiving adjuvant hormonal therapy or less
        than 12 months after completing adjuvant hormonal therapy may be enrolled directly in the
        trial.

        3. No prior therapy with an estrogen receptor down-regulator (e.g. fulvestrant).
        Non-protocol concurrent hormonal therapy is not allowed. Subjects must not have had prior
        therapy with agents that target EGFR. Previous, but not concomitant, therapy with
        trastuzumab (Herceptin) is allowed. Subjects must not receive trastuzumab (Herceptin)
        within 3 weeks prior to randomization.

        4. Subjects must have ECOG performance status of 0, 1, or 2. 5. Subjects must have adequate
        hematologic, hepatic, and renal function defined by the following within 4 weeks prior to
        randomization: Neutrophils > 1500/mm3 and platelets over 100,000/mm3 Total Bilirubin under
        1.25 x Institutional upper limit of normal SGPT (ALT) and SGOT (AST) under 2.5 x
        Institutional upper limit of normal if no demonstrable liver metastases or under 5 x
        Institutional upper limit of normal in the presence of liver metastases Calculated
        creatinine clearance over 30ml/min using the following formula: Ccr = (140 - age in years)
        times (weight in kgs) times 0.085 72 x serum creatinine in mg/dL INR, PT and PTT under 1.5
        x Institutional upper limit of normal.

        6. Subjects must not be receiving therapy with anticoagulants or have other
        contraindication to IM injections.

        7. Subjects must be age over 18 years. 8. Subjects must not have a history of central
        nervous system metastasis. 9. Subjects may receive concurrent radiation therapy to painful
        sites of bony disease or areas of impending fracture as long as the radiation therapy is
        initiated prior to study entry and sites of measurable disease outside the radiation
        therapy port are available to follow.

        10. Subjects must not take the following medications while enrolled in this trial:
        ketoconazole, erythromycin, verapamil.

        11. Subjects age less than 55 years must not be receiving LHRH agonists or antagonists
        within 3 months prior to randomization.

        12. Subjects who have an ocular inflammation or infection should be fully treated before
        entry into the trial.

        13. Subjects with a neuropathic keratopathy or diabetes or those with anterior basement
        membrane disease must be advised of the need for frequent ophthalmologic exams.

        14. Subjects who continue to wear contact lenses must be advised that they have an
        increased risk of ocular events. The decision to wear contact lenses should be discussed
        with the patient's treating oncologist and ophthalmologist.

        15. Subjects must not suffer from medical or psychiatric conditions that would interfere
        with protocol compliance, the ability to provide informed consent, or assessment of
        response or anticipated toxicities.

        16. Subjects must be disease-free of prior invasive malignancies for over 5 years with the
        exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
        carcinoma in situ of the cervix.