Phase I/II Study of Weekly Abraxane and RAD001 in Women With Locally Adv. or Metastatic Breast Ca

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Locally recurrent or metastatic disease
  • Not amenable to surgery or radiotherapy
• HER2/neu-negative disease

• Has ≥ 1 measurable lesion, as defined by RECIST criteria

  • No non-measurable lesions (e.g., pleural effusion or ascites) other than bone metastases

    • Bone metastases as the sole site of disease allowed provided there are ≥ 2 lytic bone lesions by x-ray, CT scan, or MRI
  • Lesions irradiated in the advanced setting are not considered sites of measurable disease unless clear tumor progression has been documented in these lesions since the completion of radiotherapy
• No bilateral diffuse lymphangitis carcinomatosa of the lung (> 50% of lung involvement) or evidence of liver metastases estimated as involving > one third of the liver by sonogram and/or CT scan
• No unstable CNS metastases
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 9 g/dL
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN in patients with liver metastases)
• INR < 1.5 times ULN
• Serum creatinine ≤ 1.5 mg/dL
• Fasting serum cholesterol ≤ 300 mg/dL (or 7.75 mmol/L) (levels outside this threshold allowed provided statin therapy is initiated)
• Fasting triglycerides ≤ 2.5 times ULN (levels outside this threshold allowed provided statin therapy is initiated)
• Not pregnant or nursing
• Negative pregnancy test

• Fertile patients must use effective contraception

  • Oral, implantable, or injectable contraceptives are not considered effective contraception
• No ascites or encephalopathy due to liver disease
• No neuropathy ≥ grade 2

• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus, including any of the following:

  • Ulcerative disease
  • Uncontrolled nausea, vomiting, or diarrhea
  • Malabsorption syndrome
• No active, bleeding diathesis
• No known HIV seropositivity
• No known hypersensitivity to everolimus or sirolimus (rapamycin), paclitaxel albumin-stabilized nanoparticle formulation, or lactose
• No history of noncompliance to medical regimens

• No severe and/or uncontrolled medical condition or other condition that could affect study participation, including any of the following:

  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia
  • Severely impaired lung function
  • Active (acute or chronic) or uncontrolled infections or disorders
  • Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by study treatment
  • Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
• No other malignancies within the past 5 years, except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• Prior systemic endocrine therapy for advanced breast cancer allowed

• No prior chemotherapy for advanced breast cancer

  • Prior adjuvant chemotherapy allowed
• No prior small bowel resection
• More than 5 days since prior strong CYP3A inhibitors or inducers (e.g., rifabutin, rifampin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, or telithromycin)
• More than 30 days since prior radiotherapy and recovered (alopecia allowed)
• Prior localized radiotherapy for analgesic purposes allowed provided radiotherapy has been completed and the patient's condition is stabilized
• No prior radiotherapy to ≥ 25% of the bone marrow
• More than 30 days since prior investigational drugs
• More than 1 week since prior and no concurrent immunization with attenuated live vaccines
• No concurrent oral anti-vitamin K medication, except low-dose coumadin

• No concurrent systemic steroids or other immunosuppressive agents as chronic therapy

  • Topical applications, inhaled sprays, eye drops, or local injections allowed
  • A short duration (< 2 weeks) of systemic corticosteroids allowed
• No concurrent hormone replacement therapy, topical estrogens (including any intra-vaginal preparations), megestrol acetate, or selective estrogen-receptor modulators (e.g., raloxifene)
• No other concurrent investigational or anticancer agents
• Concurrent antiangiogenic agents allowed
• Concurrent bisphosphonates allowed