Inclusion Criteria:

- Diagnosis of recurrent or metastatic SCCHN or any site except lip, thyroid, salivary gland, or nasopharynx.

- No known FDA-approved therapy available that's expected to prolong survival by greater than 3 months.

- Tumors with at least one of the following known mutations in the PI-3K signaling pathway, via assays performed in a CLIA-approved setting (Foundation Medicine FoundationOne test will be used. This assay uses a cut-off of 5% allele fraction for mutations. Allele fraction will be requested on each sample):

1. PIK3CA,

2. PIK3CG,

3. PIK3R1, PIK3R5 and PIK3AP1 (regulatory subunits),

4. AKT and mTOR, or

5. PTEN Note: PIK3CA amplification is not eligible.

- Prior receipt of platinum-containing chemotherapy for recurrent/metastatic disease or a history of progression of disease within 6 months of receiving platinum as part of concurrent chemoradiation.

- Disease must not be amenable to potentially curative treatment..

- Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.

- Myelosuppressive chemotherapy: At least 3 weeks since completion (6 weeks for nitrosourea)

- Biologic (anti-neoplastic agent): At least 14 days since completion of therapy with a biologic agent.

- Radiation (XRT):1 week must have elapsed from prior palliative XRT to non-target lesions.

- Adequate Bone Marrow Function Defined for all subjects (including status post SCT):

- Peripheral absolute neutrophil count (ANC) 1000/mm3; Note: must be >7 days from use of hematopoietic growth factor or 21 days from pegfilgastrim

- Platelet count 75,000/ mm3 (transfusion independent for >7 days)

- Hemoglobin 8.0 g/dL (may receive transfusions)

- Adequate Renal Function Defined As:

- Serum creatinine ≤ 1.5 x institution's ULN (upper limit of normal), or

- Creatinine clearance 50 ml/min

- Adequate Liver and Pancreatic Function Defined As:

- Total bilirubin 1.5 x upper limit of normal, and

- ALT or AST 5 x upper limit of normal, and

- Albumin 2 g/dL

- Adequate Central Nervous System Function Defined As:

- Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled.

Exclusion Criteria:

- Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.

- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac [including life threatening arrhythmias], hepatic, or renal disease).

- Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia or long-term radiation toxicity (radiation related toxicity 3 months or greater after radiation exposure).

- Presence of cardiac impairment defined as:

- Prior history of cardiovascular disease including heart failure that meets New York Hearth Association (NYHA) class III and IV definitions; OR

- History of myocardial infarction/active ischemic heart disease within one year of study entry; OR

- Uncontrolled dysrhythmias; OR

- Poorly controlled angina.

- Participation in a trial of an investigational agent within the prior 30 days.

- Pregnant or breast-feeding females.

- History of other malignancies except curatively excised carcinoma in situ of the cervix, non-melanomatous skin carcinoma or superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for 3 years. Other cases will be reviewed and possibly allowed if discussed with and approved by the Principal Investigator.

- Patients receiving therapeutic doses of warfarin.

- Blood pressure greater than 170/90 or two standard deviations from normal based on age and weight nomogram on three separate measurements.