Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

Inclusion Criteria:

* Stage III/IV, locally advanced, biopsy proven squamous cell cancer of the head and neck that undergo chemoradiation as their primary treatment with curative intent.
* Oropharynx (HPV positive and HPV negative), hypopharynx, larynx primaries, nasopharynx as well as those with documented SCC of the cervical lymph nodes, with unknown primaries.
* \>10 pack years of tobacco use
* Age ≥ 18 years
* ECOG performance status ≤ 2
* At least one site of measurable disease
* Adequate bone marrow function as shown by: ANC \> 1.5 x 109/L, Platelets \>100 x 109/L, Hb \>9 g/dL
* Total calcium (corrected for serum albumin) within normal limits
* Magnesium ≥ the lower limit of normal
* Potassium within normal limits for the institution.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range
* Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
* Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
* Serum amylase ≤ ULN
* Serum lipase ≤ ULN
* Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
* Signed informed consent
* INR ≤ 2

Exclusion Criteria:

* Distant metastatic disease
* Less than or equal to 10 pack years of tobacco history
* Received prior chemotherapy
* Received prior radiation to the head and neck or adjacent anatomical site
* Received prior treatment with a P13K inhibitor.
* Known hypersensitivity to BKM120 or to its excipients
* Acute or chronic liver, renal disease or pancreatitis
* Mood disorders ≥ CTCAE grade 3
* Diarrhea ≥ CTCAE grade 2
* Active cardiac disease
* History of cardiac dysfunction including any of the following:
* Patient has poorly
* Impairment of gastrointestinal (GI) function
* Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.
* Chronic treatment with steroids or another immunosuppressive agent.
* Herbal medications and certain fruits within 7 days prior to starting study drug.
* Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix B for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed).
* Undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
* Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
* Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.
* Known diagnosis of human immunodeficiency virus (HIV) infection
* History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix