Akt Inhibitor MK2206 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
Condition: Recurrent Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Nasopharyngeal Carcinoma; Recurrence
Intervention: Akt inhibitor MK2206
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well Akt inhibitor MK2206 works in treating patients with
      recurrent or metastatic head and neck cancer. Akt inhibitor MK2206 may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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