Phase I/II Study of Weekly Abraxane and RAD001 in Women With Locally Advanced or Metastatic Breast Cancer. A Study of the Cancer Institute of New Jersey Oncology Group (CINJOG)
Inclusion Criteria
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