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