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