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