Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer
Condition: Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Akt Inhibitor MK2206; Anastrozole; Goserelin Acetate; Laboratory Biomarker Analysis; Neoadjuvant Therapy; Pharmacological Study; Therapeutic Conventional Surgery
Intervention description: Given PO; Given PO; Given SC; Correlative studies; Given before standard-care surgery; Correlative studies; Undergo standard-care surgery
Intervention MeSH terms: Anastrozole; Goserelin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well Akt inhibitor MK-2206 (MK-2206) and anastrozole with or
      without goserelin acetate works in treating patients with stage II-III breast cancer. MK-2206
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
      Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole and
      goserelin acetate may fight breast cancer by blocking the use of estrogen by the tumor cells.
      Giving MK-2206, anastrozole, and goserelin acetate together may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical T2-T4c, any N, M0 invasive ER+ (Allred score of 6-8) and HER2 negative (0 or
             1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] negative
             for amplification) breast cancer, by American Joint Committee on Cancer (AJCC) 7th
             edition clinical staging, with the goal being surgery to completely excise the tumor
             in the breast and the lymph node;

               -  Note: if the patient has invasive or ductal carcinoma in situ (DCIS) in the
                  contralateral breast the patient is not eligible for this study

          -  >= 1 measurable lesion that is palpable, its size can be measured by bi-dimensional
             tape, ruler or caliper technique, and the minimum size of the largest tumor diameter
             is greater than 2.0 cm by imaging or physical examination

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          -  Life expectancy > 4 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             institutional ULN

          -  Creatinine =< ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with
             creatinine above institutional normal

          -  Patient with diabetes mellitus: fasting glucose =< 120 mg/dL and hemoglobin A1c
             (HbA1c) =< 8%

          -  Negative serum pregnancy test =< 7 days prior to pre-registration for women of
             childbearing potential

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patient is postmenopausal or premenopausal

               -  NOTE: postmenopausal women, verified by

                    -  Bilateral surgical oophorectomy, or

                    -  No spontaneous menses >= 1 year or

                    -  No menses for < 1 year with follicle stimulating hormone (FSH) and estradiol
                       levels in postmenopausal range, according to institutional standards or

               -  Premenopausal women, verified by:

                    -  Regular menses or

                    -  FSH and estradiol levels in premenopausal range, according to institutional
                       standards

          -  Willingness to provide biologic samples for PIK3CA sequencing and correlative studies

          -  Positive for PIK3CA mutation based on central laboratory testing

          -  In premenopausal women, serum estradiol level in postmenopausal range =< 7 days prior
             to registration

        Exclusion Criteria:

          -  Any of the following for treatment of this cancer including:

               -  Surgery

               -  Radiation therapy

               -  Chemotherapy

               -  Biotherapy

               -  Hormonal therapy

               -  Investigational agent prior to study entry

          -  Receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MK-2206 or other agents used in this study

          -  Prior axillary lymph node sampling (sentinel lymph node biopsy or axillary lymph node
             dissection); NOTE: fine needle aspiration (FNA) of axillary lymph node is acceptable

          -  Invasive cancer or DCIS in the contralateral breast

          -  Receiving any medications or substances that are strong inhibitors or inducers of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4);

               -  NOTE: oxidative metabolism of MK-2206 in human liver microsomes is catalyzed
                  primarily by CYP3A4, although direct glucuronidation also occurs; at least 7 days
                  washout period is required in patients who were previously taking strong
                  inhibitors or inducers of CYP.450 3A4; patients who are currently taking moderate
                  inhibitors or inducers of CYP450 3A4 are encouraged to switch to other
                  medications that do not interact with CYP450 3A4

          -  Corrected QT interval (QTc) prolongation (defined as a QTc interval > 480 msec) or
             other significant electrocardiogram (ECG) abnormalities

          -  Receiving any medications or substances with risk of torsades de pointes; Note:
             medications or substances on the list "Drugs with Risk of Torsades de Pointes" are
             prohibited; medications or substances on the list "Drugs with Possible or Conditional
             Risk of Torsades de Pointes" may be used while on study with extreme caution and
             careful monitoring

          -  Uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Uncontrolled symptomatic cardiac arrhythmia

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Women of childbearing potential who are unwilling to employ adequate
                  contraception

               -  NOTE: breastfeeding should be discontinued if the mother is treated with MK-2206;
                  women of childbearing potential 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

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy; NOTE: HIV-positive patients on combination antiretroviral therapy are
             ineligible; in addition, these patients are at increased risk of lethal infections
             when treated with marrow-suppressive therapy

          -  Evidence of inflammatory cancer (clinical presentation of skin erythema involving more
             than one third of the breast or pathological evidence of dermal lymphatic involvement)

          -  Patients with known metastatic disease are excluded

          -  Current use of therapeutic anticoagulation therapy

          -  Previous excisional biopsy of the breast cancer

          -  Any condition (e.g., gastrointestinal tract disease resulting in an inability to take
             oral medication or a requirement for intravenous [IV] alimentation, prior surgical
             procedures affecting absorption) that impairs patients ability to swallow MK-2206
             tablets