Clinical trial NCT00574366 (phase 1, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: erlotinib, rad001
SMILES: COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2, [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:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed adenocarcinoma of the breast

          -  Evaluable metastatic disease (no need for measurable disease)

          -  Must have had anthracycline therapy in the adjuvant setting or failed anthracycline
             treatment in the metastatic setting

               -  Total cumulative dose of lifetime exposure of doxorubicin not greater than 360
                  mg/m^2 or epirubicin not greater than 640 mg/m^2

          -  Must have failed previous taxane (paclitaxel or docetaxel) therapy, defined as:

               -  Taxane use in the adjuvant setting with metastatic relapse within 12 months of
                  therapy

               -  Progression on taxane therapy in the metastatic setting

               -  Discontinuation of taxane therapy in the metastatic setting secondary to lack of
                  resolution of ≥ grade 2 toxicity

          -  No symptomatic brain metastases

               -  Patients with a history of brain metastases are eligible provided they are
                  clinically stable and not taking steroids or therapeutic anticonvulsants that are
                  CYP3A4 modifiers

               -  Patients with asymptomatic brain metastasis are eligible provided they are not on
                  prophylactic anticonvulsants that are CYP3A4 modifiers

          -  Hormone receptor status not specified

        PATIENT CHARACTERISTICS:

        Inclusion criteria

          -  Menopausal status not specified

          -  ECOG performance status 0-1

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  SGOT and SGPT ≤ 2.5 times ULN

          -  Albumin > 30 g/L

          -  Creatinine ≤ 1.5 upper limit of normal

          -  INR normal provided the patient is not on warfarin therapy

          -  Not pregnant or nursing

          -  Negative pregnancy test for premenopausal patients

          -  Fertile patients must use effective barrier method contraception during and for 3
             months after completion of study treatment

          -  Patients must be disease-free of prior invasive cancers for > 5 years with the
             exception of basal cell or squamous cell cancer of the skin or cervical carcinoma in
             situ

        Exclusion criteria

          -  Serious or non-healing active wound, ulcer, or bone fracture

          -  Known human immunodeficiency virus positivity

          -  Uncontrolled intercurrent illness including, but not limited to, any of the following

               -  Ongoing or active infection requiring parenteral antibiotics

               -  Impairment of lung function (COPD, lung conditions requiring oxygen therapy)

               -  Symptomatic congestive heart failure (New York Heart Association class III or IV
                  heart disease)

               -  Unstable angina pectoris or myocardial infarction within the past 6 months

               -  Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg or diastolic
                  blood pressure > 100 mm Hg, found on two consecutive measurements separated by a
                  1-week period despite adequate medical support)

               -  Clinically significant cardiac arrhythmia (multifocal premature ventricular
                  contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or
                  requires treatment)

               -  Uncontrolled diabetes

               -  Psychiatric illness/social situations that would compromise patient safety or
                  limit compliance with study requirements including maintenance of a
                  compliance/pill diary

        PRIOR CONCURRENT THERAPY:

        Inclusion criteria

          -  See Disease Characteristics

          -  Prior trastuzumab (Herceptin®) in the first-line treatment of metastatic breast cancer
             is required for patients who have HER2/neu overexpressing tumors

          -  More than 6 months since prior cardiac angioplasty or stenting

          -  Use of endocrine therapy (i.e., aromatase inhibitors, fulvestrant, tamoxifen or
             ovarian ablation) in the first-line treatment of metastatic breast cancer is required
             for patients who have estrogen receptor and or progesterone receptor expressing tumors

               -  Concurrent endocrine therapy is not allowed

          -  Patients may receive concurrent radiotherapy to painful bone metastases or areas of
             impending bone fracture as long as radiotherapy is initiated prior to study entry

               -  Patients who have received prior radiotherapy must have recovered from toxicity
                  induced by this treatment

          -  More than 3 weeks since prior chemotherapy, biological or hormonal therapy while on
             protocol therapy.

          -  No other concurrent antineoplastic or antitumor agents, including chemotherapy,
             radiotherapy, immunotherapy, or hormonal anticancer therapy

        Exclusion criteria

          -  More than 3 prior chemotherapy treatments in the metastatic setting

               -  This restriction does not include endocrine therapies or single agent biologic
                  therapies (i.e., trastuzumab [Herceptin®])

          -  Use of steroids or immunosuppressants

          -  Use of CYP3A4 modifiers

          -  Concurrent therapy with trastuzumab (Herceptin®)

          -  Use of growth support factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF],
             recombinant erythropoietin) during the phase I portion of the study

          -  Other concurrent investigational agents