A Phase I Study of Cisplatin, Paclitaxel, and RAD001 Patients With Metastatic Breast Cancer
Inclusion Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive mammary carcinoma
- Stage IV disease
- No locally recurrent breast cancer
- Patients with HER2/neu overexpressing tumors must have received prior trastuzumab
(Herceptin®) in first-line treatment of metastatic breast cancer
- Patients with estrogen receptor- or progesterone receptor-expressing tumors must have
received prior endocrine therapy (i.e., aromatase inhibitors, fulvestrant, tamoxifen,
or ovarian ablation) in first-line treatment of metastatic breast cancer
- No symptomatic brain metastases
- Patients with a history of brain metastases must be clinically stable and not
taking steroids or therapeutic anticonvulsants that are CYP3A4 modifiers
- Patients with asymptomatic brain metastases on prophylactic convulsants that are
CYP3A4 modifiers are not eligible
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG performance status 0-1
- Life expectancy ≥ 6 months
- ANC ≥ 1000/mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN (3 times ULN if liver metastasis present)
- SGOT and SGPT ≤ 1.5 times ULN (3 times ULN if liver metastasis present)
- Alkaline phosphatase ≤ 3 times ULN if liver metastasis present
- Able to swallow and retain oral medication
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment
- Must be disease-free from prior invasive cancers for > 5 years with the exception of
completely resected basal cell or squamous cell carcinoma of the skin or successfully
treated cervical carcinoma in situ
- No malabsorption syndrome, disease significantly affecting gastrointestinal function,
or ulcerative colitis
- No uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring parenteral antibiotics
- Impairment of lung function (i.e., chronic obstructive pulmonary disease or lung
conditions requiring oxygen therapy)
- Symptomatic New York Heart Association class III-IV congestive heart failure
- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within
the past 6 months
- Uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic
BP > 100 mm Hg)
- Clinically significant cardiac arrhythmia (i.e., multifocal premature
ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia that
is symptomatic or requires treatment)
- Uncontrolled diabetes
- Psychiatric illness/social situations that would preclude compliance with study
requirements
- No known history of uncontrolled or symptomatic neuropathy ≥ grade 2
- No hypersensitivity to paclitaxel, or drugs using the vehicle Cremophor, Chinese
hamster ovary cell products, or other recombinant human antibodies
Exclusion Criteria:
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from all prior treatment
- Must not have exceeded a total cumulative dose of life-time exposure of doxorubicin
hydrochloride ≤ 360 mg/m² or epirubicin hydrochloride ≤ 640 mg/m²
- At least 2 weeks since other prior investigational drugs
- No prior resection of the stomach or small bowel
- No more than 4 prior chemotherapy regimens in the metastatic setting
- This restriction does not include endocrine therapies or single agent biologic
therapies (i.e., trastuzumab)
- Concurrent radiotherapy to painful bone metastases or areas of impending bone
fracture allowed as long as radiotherapy is initiated prior to study entry
- No concurrent trastuzumab
- No concurrent endocrine therapy
- No concurrent CYP3A4 modifiers
- No concurrent herbal supplement
- No other concurrent anticancer therapy (chemotherapy, radiotherapy, surgery,
immunotherapy, hormonal therapy, or biological therapy)