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Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Alisertib with or without Fulvestrant in Treating Patients with Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer

This phase II trial studies how well alisertib with or without fulvestrant works in treating patients with endocrine-resistant breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread to other places in the body (metastatic). Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells or reducing the amount of estrogen made by the body. Giving alisertib with or without fulvestrant may work better in treating patients with breast cancer.
Not Available
Phase II
Not Available
Not Available
Mayer, Ingrid
Vanderbilt University


18 Years
Inclusion Criteria:


Post-menopausal defined as * Age >= 60 and amenorrhea > 12 consecutive months OR * Previous bilateral oophorectomy OR * Age 12 consecutive months and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard * NOTE: If FSH level not within post-menopausal range according to institutional standard, but there is other evidence of post-menopausal status, exceptions may be granted by the principal investigator (PI)

Histologic proof of metastatic or locally advanced, unresectable breast cancer

History of ER positive (+) (>= 10% of cells positive on hematoxylin and eosin stain [H&E]), HER2 negative (?) breast cancer disease, either as a * History of primary, operable ER+/HER2? invasive breast cancer OR * History of de novo metastatic breast cancer that is ER+/HER2? ** Note: HER2? (negative) disease defined as one of the following: *** HER2 immunohistochemistry (IHC) expression of 0, 1+ and in-situ hybridization (ISH) non-amplified *** HER2 IHC expression of 0, 1+ and ISH not done *** HER2 IHC expression of 2+ and ISH non-amplified *** IHC not done and ISH non-amplified; Note: supporting documentation such as a pathology report from their primary diagnosis that indicates ER+/Her2- invasive breast cancer or a biopsy report of de novo metastatic breast cancer that is ER+/HER2? should be submitted through the RAVE database

Prior treatment * No more than two prior chemotherapy regimens in the metastatic setting * Prior treatment with fulvestrant in the metastatic setting is required, except for patients with a history of ER-negative metastatic breast cancer * Unlimited prior endocrine therapy regimens in the metastatic setting are allowed * No prior treatment with an aurora Kinase inhibitor (either an aurora A or pan-aurora kinase inhibitor)

Disease that is measurable where: * A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) * A malignant lymph node is considered measurable if its short axis is >= 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm); Note: tumor lesions in a previously irradiated area are not considered measurable disease; Note: disease that is measurable by physical examination only is not eligible

No history of tumors involving spinal cord or heart

Fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment * EXCEPTION: neuropathies – if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible

Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1

No requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes

Willing to limit daily alcohol intake to the following: one 12-oz glass of beer, one 6-oz glass of wine, or one 1.5-oz portion of 80-proof alcohol

No uncontrolled intercurrent illness including, but not limited to: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Uncontrolled symptomatic cardiac arrhythmia * Uncontrolled hypertension (defined as blood pressure > 160/90)

No history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease, or requirement for supplemental oxygen

No other active second malignancy other than non-melanoma skin cancers and in situ cervical cancers within 5 years of registration * NOTE: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 5 years prior to registration

Ability to provide written informed consent

Willing to return to enrolling institution for follow-up during the active treatment; event monitoring following completion of therapy may occur outside the enrolling institution

No history of myocardial infarction =
No prior allogeneic bone marrow or organ transplantation

No known clinical finding or suspicion of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Able to swallow oral medication

No known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib; examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease

No visceral crisis: Visceral crisis is moderate-to severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease

Willing to undergo a biopsy of a metastatic site of breast disease for central laboratory determination of ER and correlative research purposes * NOTE: If insufficient or no tissue is obtained by the pre-registration biopsy, an archival tissue specimen (preferably from a metastatic site) must be available to submit for Central Laboratory ER determination prior to registration


Central Laboratory ER determination completed

Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =
Platelet count >= 100,000/mm^3 (obtained =
Hemoglobin >= 9.0 g/dL (obtained =
Total bilirubin =
Alanine transaminase (ALT) =
Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula (obtained =
ECOG performance status: 0 or 1

Life expectancy of >= 6 months

Willing to provide blood and tissue for correlative research purposes

Exclusion Criteria:


Any of the following therapies prior to registration: * Chemotherapy =
Administration of myeloid growth factors or platelet transfusion =
Systemic infection requiring intravenous (IV) antibiotic therapy =
Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort =
Require constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes

Development of visceral crisis since pre-registration. * NOTE: Visceral crisis is moderate-to-severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease.

History of brain metastases

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