A Phase II Study of MK-2206 (NSC-749607) as Second Line Therapy for Advanced Gastric and Gastroesophageal Junction Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the stomach or
gastroesophageal (GE) junction

- Disease that has progressed after first-line regimen or is recurrent within the
past 6 months after adjuvant therapy

- Measurable disease by computed tomography (CT) scans or magnetic resonance imaging
(MRI) within the past 28 days

- No known brain metastases

- More than 3 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C)

- No prior PI3, AKT, or Mtor inhibitor for any reason

- Recovered to =< grade 1 toxicities from prior therapy

- No concurrent or plan to receive any other investigational agents

- Able to tolerate oral medications

- No malabsorption or chronic diarrhea (>= grade 2)

- No feeding tube

- Hemoglobin >= 9 g/dL

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelet count >= 100,000/mcL

- Total bilirubin =< institutional upper limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x
institutional upper limit of normal (IULN) (=< 5.0 times IULN for patients with liver
metastases)

- Serum creatinine =< IULN OR calculated creatinine clearance > 50 mL/min

- International normalized ratio (INR) =< 1.2 (unless taking therapeutic warfarin)

- Fasting blood sugar =< 150 mg/dL

- Hemoglobin A1C < 7%

- QTcF < 450 msec (male) or QTcF < 470 msec (female)

- Zubrod performance status 0-1

- None of the following:

- History of congenital long QT syndrome

- New York Heart Association (NYHA) class III or IV heart failure

- History of myocardial infarction within the past 6 months

- Uncontrolled dysrhythmia

- Poorly controlled angina

- Resting heart rate =< 50 bpm (bradycardia)

- At least 2 weeks since prior and no concurrent drugs that are strong inducers or
inhibitors of CYP3A4

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- No concurrent combination antiretroviral therapy for human immunodeficiency virus
(HIV)-positive patients

- Patient must not be pregnant or nursing because of the risk of fetal or infant harm;
women/men of reproductive potential must have agreed to use two forms of
contraception for the duration of protocol treatment and for one month after
discontinuation of MK-2206; a woman is considered to be of "reproductive potential"
if she has had menses at any time in the preceding 12 consecutive months; in addition
to routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a side
effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or
bilateral tubal ligation; however, if at any time a previously celibate patient
chooses to become heterosexually active during the time period for use of
contraceptive measures outlined in the protocol, he/she is responsible for beginning
contraceptive measures

- More than 5 years since another malignancy except adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or
II cancer for which the patient is currently in complete remission

- All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines