Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

PRIMARY OBJECTIVES:

I. To determine the confirmed response rate of patients with progressive,
recurrent/metastatic adenoid cyst carcinoma (ACC) treated with v-akt murine thymoma viral
oncogene homolog 1 (Akt) inhibitor MK2206 (MK-2206).

SECONDARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS), overall survival (OS), and
safety/tolerability for MK-2206 in these patients.

TERTIARY OBJECTIVES:

I. To explore potential genetic/cytogenetic/histopathologic predictors of clinical outcome
(i.e., response, PFS, OS) to MK-2206.

II. To explore the hypothesis that MK-2206-mediated Akt inhibition and downregulation of
v-myb avian myeloblastosis viral oncogene homolog (c-myb) protein levels in ACC tumors
correlates to clinical outcome (i.e., response, PFS, OS).

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly for 4 weeks. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up every 6 months for up to 3 years.

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

- 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 oncologist's best judgment and does not have to
meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria

- 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 least 6 weeks prior to registration; NOTE: any number of prior
chemotherapy regimens is allowed, including no prior treatment

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (equivalent to
Karnofsky >= 50%)

- Leukocytes >= 3,000/mm^3

- Absolute neutrophil count >= 1,000/mm^3

- Platelets >= 75,000/mm^3

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

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

- Creatinine =< ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with
creatinine levels above ULN

- 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

Exclusion Criteria:

- Patients who have received prior treatment with phosphatidylinositol-4,5-bisphosphate
3-kinase, catalytic subunit alpha (PI3K), v-akt murine thymoma viral oncogene homolog
1 (Akt), or mechanistic target of rapamycin (serine/threonine kinase) (mTOR)
inhibitors for recurrent/metastatic ACC

- Patients who are receiving any other investigational agents

- Patients with known brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MK-2206 or other agents used in the study

- Patients receiving any medications or substances that are major inhibitors or inducers
of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4)

- Diabetic patients with glycated hemoglobin (HbA1c) levels of greater than 8%; NOTE:
preclinical studies demonstrated the potential of MK-2206 for induction of
hyperglycemia in all preclinical species tested; 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 Fridericia corrected QT (QTcF) > 450 msec (male) or QTcF > 470
msec (female) will exclude patients from entry on study; NOTE: medications that may
cause QTc interval prolongation should be avoided by patients entering on trial

- 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

- Pregnant women; NOTE: 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; should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study,
she should inform her treating physician immediately

- Breastfeeding should be discontinued if the mother is treated with MK-2206

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

- Other active malignancy, other than indolent malignancies which the investigator
determines are unlikely to interfere with treatment and safety analysis