Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction Cancer

PRIMARY OBJECTIVES:

I. To estimate the overall survival (OS) for patients with advanced gastric and
gastroesophageal junction (GEJ) adenocarcinoma treated with MK-2206 (Akt inhibitor MK2206).

SECONDARY OBJECTIVES:

I. To estimate the progression free survival (PFS) in this patient population. II. To
estimate the response rate (confirmed and unconfirmed complete response [CR] and partial
response [PR] by Response Evaluation Criteria In Solid Tumors [RECIST] 1.1) in this patient
population.

III. To assess the frequency and severity of toxicity associated with this regimen.

OUTLINE (CLOSED TO ACCRUAL 05/01/13):

Patients receive Akt inhibitor MK2206 orally (PO) every other day on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed adenocarcinoma of the
stomach or gastroesophageal (GE) junction that has progressed after first-line
treatment, or is recurrent within 6 months after receiving adjuvant therapy; patients
must have had exactly one prior systemic treatment regimen; previous adjuvant
(chemotherapy [chemo]) radiotherapy is permitted; prior chemotherapy given
concurrently with radiation for radiosensitization is not considered one prior
systemic regimen

- Patients must have measurable disease; computed tomography (CT) scans or magnetic
resonance imaging (MRIs) used to assess measurable disease must have been completed
within 28 days prior to registration; CT scans or MRIs used to assess non-measurable
disease must have been completed within 42 days prior to registration; all disease
must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)

- Patients must not have known brain metastases

- Patients must not have received chemotherapy or radiotherapy within 3 weeks (6 weeks
for nitrosoureas or mitomycin C) prior to registration

- Patient must not have received prior treatment with a phosphatidylinositol 3 (PI3),
v-akt murine thymoma viral oncogene homolog 1 (AKT) or mechanistic target of
rapamycin (Mtor) inhibitor for any reason

- All toxicities from prior therapy must have resolved to =< grade 1 (Common
Terminology Criteria for Adverse Events [CTCAE] version 4.0) prior to registration

- Patients must not be receiving or planning to receive any other investigational
agents

- Patients must be able to tolerate oral medications and must not have malabsorption or
chronic diarrhea (CTCAE version 4.0 grade 2 or higher); administration through a
feeding tube is not permitted

- Hemoglobin >= 9 g/dL

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

- Platelets >= 100,000/mcL

- Total bilirubin =< institutional upper limit of normal (IULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 x
IULN; patients with liver metastases must have AST and ALT =< 5 x IULN

- Patients must have adequate kidney function as evidenced by at least ONE of the
following:

- Serum creatinine (mg/dL) =< IULN obtained within 14 days prior to registration

- Calculated creatinine clearance > 50 ml/min; the serum creatinine value used in
the calculation must have been obtained within 14 days prior to registration

- Patients must have international normalized ratio (INR) =< 1.2 unless taking
therapeutic doses of warfarin; this result must be obtained within 14 days prior to
registration

- Patients must have fasting blood sugar =< 150 mg/dL within 28 days prior to
registration

- Patients must have hemoglobin A1C < 7% within 28 days prior to registration

- Patients must have an electrocardiogram (ECG) within 28 days prior to registration;
patients must have corrected QT interval (QTcF) (by Fridericia's calculation) < 450
msec (male) or < 470 msec (female)

- Patients must have a Zubrod performance status of 0-1

- Patient must not have any of the following: a history of congenital long QT syndrome;
use of concomitant medications that could prolong the QTc interval; New York Heart
Association class III or IV heart failure; history of myocardial infarction within 6
months prior to registration; uncontrolled dysrhythmias; poorly controlled angina;
resting heart rate =< 50 bpm (bradycardia)

- Patients must not be receiving concurrent treatment with drugs that are strong
inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4
(CYP3A4); patients must be able to safely discontinue treatment with these agents for
>= 2 weeks prior to beginning protocol therapy

- Patient must not have 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

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible

- Patient must not be pregnant or nursing; 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

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease free for five years

- 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