Multicenter Phase II Study of MK-2206 in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma

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