Akt Inhibitor MK2206 in Treating Patients With Advanced Breast Cancer
Condition: Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Akt Inhibitor MK2206; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given orally (PO) weekly, starting (dose 0) at 200 mg; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with
      breast cancer cancer that has spread to other places in the body and usually cannot be cured
      or controlled with treatment. Akt inhibitor MK2206 may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed breast cancer, with
             diagnosed or suspected metastatic, inoperable locally advanced breast cancer, or
             inoperable locally recurrent breast cancer

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as > 20 mm with conventional
             techniques or as > 10 mm with spiral computed tomography (CT) scan

          -  Patients who have failed to respond to at least one line of systemic therapy are
             eligible for MK2206 therapy; if the patient has a human epidermal growth factor
             receptor 2 (HER2) positive tumor, it is expected that they will have received at least
             one HER2-targeted therapy in the metastatic setting; if the patient has an estrogen
             receptor positive (ER+) tumor, it is expected that they will have received at least
             one ER-targeted therapy in the metastatic setting; patients can be enrolled for
             molecular screening while on another therapy if the patient is interested in MK2206
             therapy upon progression

          -  Archived primary tumor biopsies or surgical specimens, or biopsies of recurrence or
             metastasis, will be available for PIK3CA/Akt mutational analysis and PTEN analysis;
             patients with surgical samples, or core/punch biopsies available, will be eligible for
             testing for PIK3CA/Akt status as well as PTEN testing; the most recent sample will be
             preferred (i.e. in patients with metastatic disease, metastases samples are preferred
             over archival primary tumor and in patients with local recurrences a biopsy of the
             recurrence is preferred over archival primary tumor); NOTE: PIK3CA or Akt mutation
             status can be determined on fine needle aspirate (FNA) samples, but PTEN status cannot
             as stroma and endothelial cells are used as internal controls and PTEN testing has not
             been validated on FNA samples; thus patients with only FNA samples and no tissue
             blocks available will be considered to be eligible for screening for PIK3CA/Akt
             mutations and will be enrolled onto the study only if they are found to have PIK3CA
             mutations or Akt mutations; patients whose tumors have already been tested in the
             Clinical Laboratory Improvement Amendments (CLIA) environment and have been found to
             have a PIK3CA mutation or Akt mutation or PTEN loss by immunohistochemistry (IHC) or
             PTEN mutation will be eligible for treatment; patients whose tumors have been tested
             in the research environment and found to have a PIK3CA mutation or Akt mutation or
             PTEN loss or PTEN mutation will have their marker status confirmed in the CLIA
             environment

          -  Patients whose tumors have already been tested in the CLIA environment and have been
             found to have a PIK3CA mutation or Akt mutation or PTEN loss or mutation will be
             eligible for treatment; patients whose tumors have been tested in the research
             environment and found to have a PIK3CA mutation or Akt mutation or PTEN loss or
             mutation will have their marker status confirmed in the CLIA environment.

          -  Patient will have a tumor suitable for FNA and/or core/punch biopsy for research
             purposes

          -  Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Absolute neutrophil count (ANC) >= 1,000/uL

          -  Platelets >= 100,000/uL

          -  Hemoglobin (Hgb) >= 9 g/dL

          -  Creatinine =< 1.5 X upper limit of normal (ULN)

          -  Prothrombin time (PT), partial thromboplastin time (PTT) =< 1.2 X ULN

          -  Total bilirubin =< 1.5 X ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN

          -  Patients of childbearing potential must have a negative serum or urine pregnancy test
             beta-human chorionic gonadotropin (hCG) within 72 hours prior to study registration

          -  Women of childbearing potential and men must use two forms of contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry, for the duration
             of study participation and also for 4 weeks after the end of therapy; 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 have completed any systemic therapy regimens and therapeutic radiation a
             minimum of 21 days prior to initiation of study therapy

          -  Ability to understand and the willingness to sign a written informed consent document

          -  >= 6 months life expectancy as documented in patient records

        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 to grade 1 or less due to agents administered more than
             3 weeks earlier

          -  Patients may have received prior investigational therapies; however, they not be
             receiving any other investigational agents concurrent with MK2206; patients must have
             completed therapy a minimum of 21 days prior to initiation of study therapy

          -  Patients may not have received treatment with another inhibitor of
             phosphatidylinositol 3 kinase (PI3K), Akt or mammalian target of rapamycin (mTOR) in
             the neoadjuvant, adjuvant or metastatic setting with the exception of rapalogs;
             patients with metastatic breast cancer, who received PI3K/Akt/mTOR inhibitors on short
             preoperative window trials (treatment for 4 weeks or less), will be eligible if the
             treatment was over 6 months prior to registration; patients must have completed
             therapies a minimum of 21 days prior to initiation of study therapy

          -  Patients with known brain metastases should be excluded from this clinical trial;
             patients will not undergo pre-treatment imaging of the brain, unless clinically
             indicated

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MK2206 or other agents used in the study

          -  Patients receiving any medications or substances that are potent inhibitors or
             inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 450 3A4) are
             ineligible; however, patients will be permitted regular dietary consumption of
             caffeine; glyburide will be allowed for the treatment of hyperglycemia

          -  Patients with diabetes or in risk for hyperglycemia should not be excluded, but
             patients with poorly controlled diabetes (glycated hemoglobin [HBA1C] > 8%) should be
             excluded

          -  Baseline corrected QT by Fridericia's formula (QTcF) > 450 msec (male) or QTcF >b470
             msec (female) will exclude patients from entry on study

          -  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

          -  Baseline bradycardia related to cardiac disease, or significant bundle branch block

          -  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

          -  Patients at high risk for coagulopathy

          -  Liver disease burden greater or equal to 50 percent

          -  Need for blood or platelet transfusion within one month from baseline laboratory
             testing as well as within treatment initiation