Akt Inhibitor MK2206 in Treating Patients With Recurrent or Advanced Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Endometrial Neoplasms; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Recurrence
Intervention: Akt Inhibitor MK2206; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with
      recurrent or advanced endometrial cancer. Akt inhibitor MK2206 may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have histologically confirmed recurrent or persistent high grade
             endometrial carcinoma with a serous component, which is refractory to curative therapy
             or established treatments; histologic confirmation of the original primary tumor is
             required

          -  All patients must have measurable disease as defined by RECIST 1.1; measurable disease
             is defined as at least one lesion that can be accurately measured in at least one
             dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
             measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper
             measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes
             must be >= 15 mm in short axis when measured by CT or MRI

          -  Patients must have had one prior chemotherapeutic regimen for management of
             endometrial carcinoma initial treatment may include chemotherapy, chemotherapy and
             radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered
             in conjunction with primary radiation as a radio-sensitizer WILL be counted as a
             systemic chemotherapy regimen

          -  Patients are allowed to receive, but are not required to receive, one additional prior
             treatment regimen (including a single chemotherapeutic, a combination of
             chemotherapeutics, or an anti-angiogenic drug such as bevacizumab) for management of
             their recurrent or persistent disease; prior hormonal therapy is allowed and does not
             count towards this prior regimen

          -  Patients must have NOT received any class of drugs targeted to the PI3K pathway (such
             has PI3K inhibitors or mTOR inhibitors) for management of recurrent or persistent
             disease

          -  Life expectancy of greater than 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic 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 subjects with creatinine levels about institutional normal

          -  Hemoglobin A1c (HgA1c) =< 7.5% and fasting blood glucose less than 130mg/dL

          -  Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue from
             the original or most recent biopsy for mutational analysis

          -  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; should a patient become pregnant or suspect she is pregnant
             while she is participating in this study, she should inform the treating physician
             immediately

          -  Toxicities of prior therapy (excepting alopecia) should be resolved to =< grade 1 per
             the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4

          -  MK-2206 is an oral medication; patients must be able to tolerate oral medications and
             not have gastrointestinal illnesses that would preclude absorption of MK-2206

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Participants 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 to =< grade 1 (excepting alopecia) from adverse events (as per the revised
             NCI CTCAE version 4) due to agents administered more than 3 weeks earlier

          -  Participants may not be receiving any other study agents

          -  Participants with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events;
             should patients develop brain metastases while on trial and have clinical benefit from
             MK-2206 otherwise, patients may continue on drug after clinical management of the
             brain metastases with the permission of the principal investigator. MK-2206 should be
             restarted between 3 and 6 weeks after the last radiation treatment

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MK-2206

          -  Patients requiring any medications or substances that are strong inhibitors or
             inducers of CYP 450 3A4 are ineligible

          -  Preclinical studies demonstrated the potential of MK-2206 for induction of
             hyperglycemia in all preclinical species tested; patients with diabetes or in risk for
             hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia
             should be well controlled on oral agents before the patient enters the trial. HgbA1c >
             7.5% or fasting glucose greater than 130mg/dL will exclude patients from entry on
             study; patients requiring insulin for control of their hyperglycemia are excluded from
             entry on this study

          -  Preclinical studies indicated transient changes in QTc interval during MK-2206
             treatment; prolongation of QTc interval is potentially a safety concern while on
             MK-2206 therapy; cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec
             (female) will exclude patients from entry on study

          -  Due to a high incidence of bradycardia by Holter monitor, preexisting bundle branch
             block or baseline bradycardia due to cardiac disease will exclude patients from
             treatment with MK-2206

          -  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; mother with MK-2206 breastfeeding should
             be discontinued if the mother is treated with MK-2206; these potential risks may also
             apply to other agents used in this study

          -  MK-2206 is an oral medication; patients who are unable to tolerate oral medication are
             not eligible; patients with signs and symptoms of bowel obstruction or with
             uncontrolled, persistent diarrhea will be excluded

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 5 years and are deemed by the investigator
             to be at low risk for recurrence of that malignancy. Individuals with the following
             cancers are eligible if diagnosed and treated within the past 5 years: breast cancer
             in situ, cervical cancer in situ, and basal cell or squamous cell carcinoma of the
             skin

          -  Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral
             therapy are ineligible

          -  Patients may not use natural herbal products or other "folk remedies" while
             participating in this study