Akt Inhibitor MK2206 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma that has recurred at locoregional and/or distant sites, and is not amenable to potentially curative radiotherapy or surgery
• Measurable disease according to the RECIST criteria
• Progressed =< 24 months of receiving one or two prior line(s) of chemotherapy for recurrent disease, of which at least one line must contain platinum drugs such as cisplatin, carboplatin or oxaliplatin
• ECOG performance status 0, 1, or 2
• Hemoglobin >= 9 g/dL
• ANC >= 1,500/μL
• Platelet count >= 100,000/μL
• Total bilirubin =< 2.5 times upper limit of normal (ULN)
• ALT =< 2.5 times ULN (=< 5 times ULN for patients with liver metastases)
• Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to donate blood for mandatory correlative research studies
• Negative (serum) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria:

• Any of the following

  • Chemotherapy =< 4 weeks prior to registration
  • Radiotherapy =< 4 weeks prior to registration
  • Nitrosoureas or Mitomycin C =< 4 weeks prior to registration
  • Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • NOTE: Prior palliative radiotherapy to bone metastases is allowed =< 4 weeks prior to registration
• Prior investigational agents =< 4 weeks prior to registration
• Symptomatic brain metastases; NOTE: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa(e) are not regarded as brain metastases and are not excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study

• Prior potent and moderate inhibitors and inducers of CYP3A4 =< 2 weeks prior to registration:

  • Drugs that are forbidden, potent inducers of CYP3A4: phenytoin, phenobarbitone, carbamazepine, barbiturate, rifampicin, St John's Wort.
  • Drugs that significantly affect metabolizing activity by way of enzyme inhibition of CYP3A4: ketoconazole, itraconazole, fluconazole, indinavir, ritonavir, erythromycin, cimetidine, clarithromycin
• Unwillingness to go off other inducers and inhibitors of CYP3A4 during the first 2 cycles of MK-2206; NOTE: avoiding these drugs is critical during the first 2 cycles of MK-2206when blood samples are being taken for the correlative study unless there is an urgent medical need and alternatives are not available
• Poorly controlled diabetes mellitus or insulin controlled diabetes; NOTE: As a general guide, patients with a fasting glucose level > 150 mg/dL (HbA1c <8%, > 8.3 mmol/L), or a random glucose level of >180mg/dL (> 10 mmol/L) is considered to have inadequately controlled diabetes and are not eligible for this study; however, such patients can become eligible in the future if their fasting glucose levels improve with medical treatment
• QTc prolongation (defined as a QTc interval > 450 msec for males and >470 msec for females) or other significant ECG abnormalities; NOTE: patients with clinically significant cardiac conduction abnormalities should be excluded, these include left bundle branch block (LBBB), 2nd or 3rd degree AV block, bifascicular block, sick sinus syndrome, Wolff-Parkinson-white syndrome, sinus bradycardia (< 50bpm); however, patients with asymptomatic right bundle branch block (RBBB) or 1st degree AV block, in the absence of known cardiac disease (e.g. coronary, valvular) are not excluded

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection,
  • Symptomatic congestive heart failure,
  • Unstable angina pectoris,
  • Uncontrolled symptomatic cardiac arrhythmia,
  • Psychiatric illness/social situations that would limit compliance with study requirements

• Diagnosed to have any of the following condition(s), and/or have undergone any one of the following procedure(s) =< 3 months prior to registration:

  • Symptomatic thrombotic or hemorrhagic cerebral vascular accident
  • Coronary bypass graft
  • Angioplasty
  • Myocardial infarction
• Patients having continuing >= grade 2 adverse events (excluding alopecia) due to agents (chemotherapy or radiotherapy) administered > 4 weeks prior to registration based on Common Terminology Criteria for Adverse Events (CTCAE version 4.0) =< grade 1

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • NOTE: because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-2206, breastfeeding should be discontinued if the mother is treated with MK-2206; women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• HIV-positive patients on combination antiretroviral therapy; NOTE: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
• Recent major surgery =< 4 weeks prior to registration (excluding the placement of vascular access), or minor surgery =< 2 weeks prior to registration
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) that impairs patients ability to swallow MK-2206 tablets