Dinaciclib and Epirubicin Hydrochloride in Treating Patients With Metastatic Triple-Negative Breast Cancer

This is an interventional treatment trial for Estrogen Receptor Negative Read More

Inclusion Criteria:

• Patients must have histologically confirmed estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; for purposes of this study, triple negative disease will be tumors that have ER/PR < 10% and HER2 =< 1+ by immunohistochemistry (IHC) or HER2 fluorescent in situ hybridization (FISH) non-amplified (ratio < 2)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients must have no more than two prior chemotherapy regimens for metastatic breast cancer; in patients who develop disease recurrence within 6 months of adjuvant or neoadjuvant chemotherapy, the adjuvant or neoadjuvant therapy will be considered one prior regimen for metastatic disease
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal limits unless clinical diagnosis of Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients must be disease free of prior malignancy for >= 5 years with the exception of curatively treated squamous cell carcinomas of the skin or carcinoma in situ of the cervix or breast
• Must have at least one site of objective measurable or evaluable disease; baseline measurements and evaluations must be obtained within 4 weeks of start of therapy
• Patients must have no history of prior therapy with dinaciclib
• Concurrent use of hormonal therapy is not permitted; concurrent radiation therapy is not permitted; bisphosphonates are allowed, provided that they were started no less than two weeks prior to initiating protocol therapy
• Patients must have completed and recovered from the effects of prior chemotherapy (< grade 2 toxicity) excluding alopecia
• Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of dinaciclib administration
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events
• Patients who are receiving any other investigational agents
• Patients with untreated brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as epirubicin or dinaciclib
• Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) are ineligible
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dinaciclib
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients who have had prior organ allograft or require immunosuppressive therapy
• Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 600 mg/m^2; patients who have received > 240 mg/m^2 of doxorubicin or > 400 mg/m^2 of epirubicin should be advised to undergo evaluation of left ventricular ejection fraction (LVEF) with echocardiogram or multi gated acquisition scan (MUGA) prior to initiating therapy
• Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or cerebral vascular accident (CVA) within 6 months of protocol registration
• LVEF < 50% by MUGA or echocardiogram (ECHO)
• Patients who have history of PR prolongation or atrioventricular (AV) block