MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

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

Inclusion Criteria:

• Patients must have histologically-confirmed operable invasive breast cancer and have undergone core needle biopsy with an anticipated surgical resection for residual disease after enrollment
• Patients must have clinical stage I-III invasive breast (invasive tumor must be clinically at least >= T1c by radiograph or palpation)
• Patients must have available tissue from core biopsies for biomarker assessment; it is recommended that at least 4 cores be performed with 12 gauge (or smaller gauge) needles; this includes cores underneath ultrasound-guidance
• Patients are planning to undergo surgical treatment with either segmental resection or total mastectomy (required: 2 doses of weekly MK-2206 prior to surgery; the first dose will be at day -9 [+/- 1 day] and second dose at day -2 [+/- 1 day] in relation to surgery [day 0])
• Patients may have a history of contralateral breast cancer, provided there is no evidence of recurrence of the initial primary breast cancer
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >= 80%)
• Leukocytes >= 3,000/ul within 28 days of registration
• Platelets >= 100,000 /uL within 28 days of registration
• Hemoglobin (Hgb) >= 9 g/dL within 28 days of registration
• Creatinine =< 1.5 x upper limit of normal (ULN) within 28 days of registration
• Prothrombin time (PT), partial thromboplastin time (PTT) =< 1.2 x ULN within 28 days of registration
• Total bilirubin =< 1.5 x ULN within 28 days of registration
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN within 28 days of registration
• Patients of childbearing potential must have a negative serum or urine pregnancy test beta-human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication
• Women of childbearing potential and men must use two forms of contraception (hormonal or 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, the patient should inform the treating physician immediately
• Patient must be able to swallow oral tablets
• Ability to understand and the willingness to sign a written informed consent document
• Patients must agree to biomarker assessment of pre-treatment diagnostic core biopsy tissue and the surgical resection tissue (i.e. excision or mastectomy); also, must agree to pre- and post-treatment fasting blood biomarker collection

Exclusion Criteria:

• Patients may not have any known evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases) or locally recurrent breast cancer
• Patients with inflammatory breast cancer are not eligible
• Patients with prior chemotherapy or radiation therapy within 6 months of study entry are not eligible (i.e. patient who have received neoadjuvant therapy are not eligible)
• Patients may not be receiving any other investigational agents, including other inhibitors of PI3K, Akt, or mammalian target of rapamycin (mTOR)
• Men diagnosed with breast cancer
• Patients may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 used in the study
• Patients with known diabetes which is poorly controlled diabetes (hemoglobin A1c [HBA1C] >= 8%) should be excluded; if patient is taking metformin, must have been taking this medication for > 3 months, as metformin is thought to impact PI3K/Akt signaling
• Baseline corrected QT interval (QTc) > 470 msec will exclude patients from entry on study; patients with a baseline bundle branch block will be excluded
• 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 MK2206
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible