A Phase II Study of AZD0530 in Hormone Receptor-Negative, Metastatic or Unresectable, Locally Advanced Breast Cancer
Inclusion Criteria:
- Histologically or cytologically confirmed carcinoma of the breast
- Unresectable disease
- Locally advanced or metastatic (American Joint Committee on Cancer [AJCC] stage
IV) disease
- Estrogen receptor-negative and progesterone receptor-negative breast cancer defined
as < 10% expression by immunohistochemistry (IHC)
- Measurable disease, defined (per Response Evaluation Criteria in Solid Tumors
[RECIST]) as ≥ 1 unidimensionally measurable lesion ≥ 20mm by conventional techniques
or ≥ 10 mm by spiral computed tomography (CT) scan
- Measurable target lesions must not be in a previously irradiated field
- Patients with locally advanced, unresectable disease must have progression of disease
following no more than one first-line chemotherapy regimen
- Patients with evidence of recurrent disease during or within 6 months after adjuvant
chemotherapy will be considered to have failed one line of chemotherapy for
metastatic disease
- Human epidermal growth factor receptor 2 (HER2)-positive patients, defined as
immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH)
amplification > 2.1, must have received trastuzumab (Herceptin®) in either the
adjuvant or metastatic setting and have had recurrence or progression of disease,
respectively
- No known brain metastases
- Male and female patients eligible
- Menopausal status not specified
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 (Karnofsky PS
60-100%)
- Life expectancy > 3 months
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Hemoglobin > 9 g/dL
- Total bilirubin normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
≤ 2.5 x institutional upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Urine protein creatinine (UPC) ratio must be ≤ 1.0
- Patients with a UPC ratio > 1.0 must have a 24-hour urine protein < 1,000 mg to
be eligible for study
- Not pregnant or nursing
- Women of child-bearing potential and men must use adequate contraception (e.g.,
hormonal or barrier method of birth control or abstinence) prior to, during, and for
8 weeks after completion of study therapy
- Able to understand and willing to sign a written informed consent document
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to AZD0530
- No QTc interval ≥ 500 msecs
- No condition that impairs the ability to swallow AZD0530 tablets, including the
following:
- Gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- No intercurrent cardiac dysfunction including, but not limited to, any of the
following:
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- History of myocardial infarction within 6 months of treatment
- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements
- No severe restrictive or obstructive lung disease according to baseline pulmonary
function studies including any of the following pulmonary function test (PFT)
parameters:
- Total lung capacity < 60%
- Forced vital capacity < 50%
- Forced expiratory volume in one second (FEV_1) < 50%
- Diffusion capacity of carbon monoxide (DLCO) < 50%
- Resting room air O_2 saturation < 92% or a decline in O_2 saturation > 4% with
exercise
- Patients with metastatic disease may have received no more than 1 prior chemotherapy
regimen
- No unresolved toxicity ≥ grade 3 from agents received more than 3 weeks earlier
- No chemotherapy, radiotherapy, or investigational therapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering study
- No luteinizing hormone-releasing hormone agonists within 4 weeks prior to study entry
- More than 7 days since prior and no concurrent use of specifically prohibited
cytochrome P 450 3A4 (CYP3A4) agents
- No concurrent megestrol acetate, even when prescribed for appetite stimulation
- No other concurrent investigational or commercial agents for the treatment of breast
cancer
- No concurrent combination antiretroviral therapy for human immunodeficiency virus
(HIV)-positive patients
- No concurrent megestrol acetate