A Trial of Concurrent Radiation Therapy, Cisplatin, and BMX-001 in Locally Advanced Head and Neck Cancer

Inclusion Criteria

• Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or oral cavity with clinical or pathologic high-risk features for whom cisplatin and radiation would be considered appropriate care.
• Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy depending on whether patients are considered post-operative high risk or unresectable/organ preservation high risk. Planned radiation treatment fields must include at least two oral sites buccal mucosa, retromolar trigone, floor of mouth, oral tongue, soft palate, hard palate) with a portion of each site receiving a minimum total of 50 Gy.
• Patients who are to undergo definitive chemoradiation must have clinically or radiographically evident measurable disease at the primary site and/or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted.
• Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions. Fine needle aspirations of the neck that are positive for squamous cell carcinoma are sufficient for diagnosis pending pathology review at participating institutions.
• For patients undergoing curative intent resection the following criteria are required:
• Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma
• Patients must have undergone gross total surgical resection within 42 days prior to registration and beginning of therapy under the clinical trial. Note: Patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection.
• Clinical or pathologic stage Stage III-IVb per the American Joint Committee on Cancer (AJCC), 7th edition.
• General history and physical examination by a radiation oncologist and medical oncologist within 4 weeks prior to enrollment.
• Examination by an ear/nose/throat (ENT) or head and neck surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to enrollment.
• Zubrod Performance Status 0-2 within 4 weeks prior to enrollment
• Complete blood count (CBC)/differential obtained within 7 days prior to starting the study drug with adequate bone marrow function, defined as follows:
• Hemoglobin ≥ 9.0 g/dl;
• Platelets ≥ 100,000 cells/mm3;
• Absolute neutrophil count (ANC) > 1, 500 cell/mm3.
• Adequate hepatic function as defined as follows:
• Total bilirubin < 2x institutional upper limit of normal (ULN) within 7 days prior to starting the study drug;
• Aspartate aminotransferase (AST) and AST <3x institutional ULN within 7 days prior to starting the study drug.
• Adequate renal function defined as follows:
• Serum creatinine < 1.5 mg/dl within 7 days prior to starting the study drug or creatinine clearance rate (CCr) ≥ 50 mL/min within 7 days prior to starting the study drug determined by 24-hour collection or estimated by Cockcroft-Gault formula:

CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

• Negative pregnancy test for women of child-bearing potential within 48 hours prior to first dose of BMX-001.
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study and until 12 months following the last study treatment.

Exclusion Criteria

• Stage I or II; T1N1 and T2N1 stage III presentations per AJCC 7th edition
• Distant metastasis
• Hypertension requiring 3 or more anti-hypertensive medications to control
• Grade ≥2 hypotension at screening
• Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precip