A PHASE II STUDY OF MK-2206 IN PATIENTS WITH PROGRESSIVE, RECURRENT/METASTATIC ADENOID CYSTIC CARCINOMA

Inclusion Criteria:

- Patients must have pathologically confirmed adenoid cystic carcinoma; confirmation
will be performed locally at each participating institution; cancers arising from
non-salivary gland primary sites are allowed

- (Salivary Gland Cancer [10039397] and Solid Tumor NOS [10029000])

- Patients must have measurable disease, 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 ≥ 2.0 cm with conventional techniques or
as ≥ 1.0 cm with spiral computed tomography (CT) scan; to be considered
pathologically enlarged and measurable, a lymph node must be > 1.5 cm in short axis
when assessed by CT scan (CT scan slice-thickness recommended to be no greater than 5
mm)

- Patients must have locally advanced and/or recurrent and/or metastatic disease not
amenable to potentially curative surgery or radiotherapy

- Patients must have increasing disease, defined as the presence of new or progressive
lesion(s) on CT/magnetic resonance imaging (MRI) within 6 months prior to study
enrollment and/or new/worsening disease-related symptoms; NOTE: This increase in
disease is to be determined in the oncologists best judgment and does not have to
meet RECIST criteria

- No patients with known brain metastases

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (equivalent to
Karnofsky ≥ 50%)

- Leukocytes ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,000/mm³

- Platelets ≥ 75,000/mm³

- Total bilirubin ≤ institutional upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamic pyruvate transaminase(SGPT) (alanine aminotransferase [ALT]) ≤ 2.5
institutional upper limit of normal

- Creatinine ≤ ULN OR creatinine clearance ≥ 60 mL/min

- Patients must be able to swallow whole tablets; NOTE: nasogastric or gastric (G) tube
administration is not allowed; tablets must not be crushed or chewed

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to MK-2206 or other agents used in the study

- No diabetic patients with HbA1c levels of greater than 8%; patients with diabetes or
at risk for hyperglycemia should not be excluded from trials with MK-2206, but the
hyperglycemia should be well controlled before the patient enters the trial

- Cardiovascular baseline QTcF > 450 msec (male) or QTcF> 470 msec (female) will
exclude patients from entry on study

- No 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, in the opinion of the
investigator, would limit compliance with study requirements

- No pregnant women; women of child-bearing potential must have a negative serum or
urine pregnancy test within 7 days prior to registration

- Women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation

- No breastfeeding

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

- No other active malignancy, other than indolent malignancies which the investigator
determines are unlikely to interfere with treatment and safety analysis

- Chemotherapy and radiation therapy must be completed at least 4 weeks prior to
registration

- If the last regimen included carmustine (BCNU) or mitomycin C, it must be
completed at least6 weeks prior to registration

- Any number of prior chemotherapy regimens is allowed, including no prior
treatment

- No patients who have received prior treatment with PI3K, Akt, or mTOR inhibitors for
recurrent/metastatic ACC

- No patients who are receiving any other investigational agents

- No patients receiving any medications or substances that are major inhibitors or
inducers of CYP450 3A4