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

• Median PFS [ Time Frame: Time of study entry to the first disease progression or death, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using Kaplan-Meier methodology.
• Overall OS [ Time Frame: Time of study entry to death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using Kaplan-Meier methodology.
• Incidence of toxicities of Akt Inhibitor MK-2206 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Time to first treatment to up to 30 days after completion of treatment ] [ Designated as safety issue: Yes ]

• Media PFS from time to study entry to the first disease progression or death using Kaplan-Meier methodology assessed up to 3 years [ Designated as safety issue: No ]
• OS from time to study entry to death due to any cause using Kaplan-Meier methodology assessed up to 3 years [ Designated as safety issue: No ]
• Safety and tolerability of MK-2206 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 from time to first treatment to up to 30 days after completion of treatment [ Designated as safety issue: Yes ]

This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with progressive, recurrent, or metastatic adenoid cyst carcinoma (cancer). Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

PRIMARY OBJECTIVES:

I. To determine the confirmed response rate in patients with progressive, recurrent/metastatic adenoid cyst carcinoma (ACC) treated with 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.

ii. To explore potential genetic/cytogenetic/histopathologic predictors of clinical outcome (i.e., response, PFS, OS) to MK-2206. (Exploratory) III. To explore the hypothesis that MK-2206-mediated Akt inhibition and downregulation of c-myb protein levels in ACC tumors correlates to clinical outcome (i.e., response, PFS, OS). (Exploratory)

OUTLINE: This is a multicenter study.

Patients receive Akt inhibitor MK2206 once weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor tissue biopsies for correlative studies. Archived tumor tissue samples may be also collected.

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

• Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
• Recurrent Salivary Gland Cancer
• Salivary Gland Adenoid Cystic Carcinoma
• Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity
• Stage IVA Salivary Gland Cancer
• Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity
• Stage IVB Salivary Gland Cancer
• Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity

• Drug: Akt inhibitor MK2206
  Given orally
  Other Name: MK2206
• Other: laboratory biomarker analysis
  Correlative studies

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