Clinical trial NCT00317720 (phase 1/phase 2, status: completed)
Conditions: breast cancer, neoplasm metastasis
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: trastuzumab, rad001
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC
Eligibility criteria:

        Inclusion Criteria:

          1. History of biopsy-proven HER-2-overexpressing breast cancer and radiographic evidence
             of metastatic disease. The HER-2 status can be determined either by
             immunohistochemistry (score, 3+) or by fluorescence in situ hybridization.

          2. History of trastuzumab resistance, defined as the development of progressive disease
             after trastuzumab-based therapy for metastatic breast cancer. Patient may not have
             received more than 2 prior trastuzumab-based regimens and one lapatinib-based regimen
             (either as single agent or in combination with chemotherapy)for metastatic breast
             cancer. Patients who develop metastatic disease during or after adjuvant or
             neoadjuvant trastuzumab are eligible.

          3. Performance status 0-2 (by Eastern Cooperative Oncology Group (ECOG) scale).

          4. Absolute neutrophil count (ANC) 1500/µl or higher; Platelets 100,000/µl or higher;
             Hemoglobin 9.0 gm/dL or higher; Serum creatinine 2.0 mg/dL or lower; Total bilirubin
             1.5 mg/dL or lower; Serum glutamic pyruvic transaminase (SGPT) up to 3* upper limit of
             normal; Alkaline phosphatase up to 3* upper limit of normal; Calcium 11.0 mg/dL or
             lower.

          5. Age 18 years or older.

          6. Patients must not be pregnant. A pregnancy test will be obtained if the patient is a
             woman of child-bearing potential, defined as a sexually mature woman who has not
             undergone a hysterectomy or who has not been naturally postmenopausal for at least 24
             consecutive months (i.e., who has had menses at any time in the preceding 24
             consecutive months).

          7. Patients must have signed an informed consent document stating that they understand
             the investigational nature of the proposed treatment.

          8. Patients must have measurable disease using Response Evaluation Criteria in Solid
             Tumors (RECIST). Measurable disease is defined as at least one lesion that can be
             accurately measured in at least one dimension with longest diameter >/= 20 mm using
             conventional techniques or >/= 10 mm with spiral computed tomography (CT) scan.

          9. Patients may not be receiving any other investigational agents, and must not have
             received investigational agents within 15 days of enrollment.

         10. Left ventricular ejection fraction determined by echocardiogram or multigated
             acquisition (MUGA) (cardiac scan) must be 50% or higher.

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          2. Prior treatment with any investigational drug within the preceding 15 days

          3. Chronic treatment with systemic steroids or another immunosuppressive agent

          4. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases, and patients diagnosed
             with brain mets or leptomeningeal disease (LMD) within 3 months.

          5. Other malignancies within the past 3 years except for adequately treated carcinoma of
             the cervix or basal or squamous cell carcinomas of the skin.

          6. A known history of HIV seropositivity

          7. Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
             nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

          8. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
             (except low dose coumadin)

          9. Patients who have received prior treatment with an mTor inhibitor.

         10. History of noncompliance to medical regimens.

         11. Patients unwilling to or unable to comply with the protocol.

         12. Patients who are receiving any other investigational agents

         13. Patients exhibiting confusion, disorientation, or having a history of major
             psychiatric illness that may impair the understanding of the informed consent.