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

Inclusion Criteria:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Clinical or pathologic stage Stage III-IVb per the American Joint Committee on Cancer
(AJCC), 7th edition.

7. General history and physical examination by a radiation oncologist and medical
oncologist within 4 weeks prior to enrollment.

8. 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.

9. Zubrod Performance Status 0-2 within 4 weeks prior to enrollment

10. 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.

11. 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.

12. 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)

13. Negative pregnancy test for women of child-bearing potential within 48 hours prior to
first dose of BMX-001.

14. 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:

1. Stage I or II; T1N1 and T2N1 stage III presentations per AJCC 7th edition

2. Distant metastasis

3. Hypertension requiring 3 or more anti-hypertensive medications to control

4. Grade ≥2 hypotension at screening

5. Requirement for concurrent treatment with nitrates or other drugs that may, in the
judgment of the treating investigator, create a risk for a precipitous decrease in
blood pressure

6. History of syncope within the last 6 months

7. Patients receiving, or unable to stop use at least 1 week prior to receiving the first
dose of BMX-001, medications listed in Section 12.2 of the protocol are not eligible.

8. Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

9. Women who are breast feeding are not eligible

10. Prior allergic reaction to cisplatin

11. Known hypersensitivity to compounds of similar chemical composition to BMX-001

12. Grade 3-4 electrolyte abnormalities (CTCAE v 4.03) except sodium, which must be ≥126
mmol/L.

13. Prior unrelated malignancy requiring current active treatment with the exception of
cervical carcinoma in situ, basal cell carcinoma of the skin, resected T1-2N0M0
differentiated thyroid cancers, invasive cancers with a 3-year disease-free interval,
Ta bladder cancers, or low and favorable intermediate risk prostate cancer.

14. Prior history of HNSCC receiving radiation or chemo-radiation.

15. Prior systemic chemotherapy for the study cancer (including neoadjuvant chemotherapy);
note that prior chemotherapy for a different cancer is allowable.

16. Prior radiotherapy that would result in overlap of radiation treatment fields with
planned treatment for study cancer.

17. Severe, active co-morbidity, defined as follows:

- Cardiovascular disease or cerebrovascular disease, for example cerebrovascular
accidents or myocardial infarction ≤ 6 months prior to study enrollment, unstable
angina, New York Heart Association (NYHA) Grade II or greater congestive heart
failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with
the potential to interfere with protocol treatment;

- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent arterial thrombosis) within 6 months prior to enrollment;

- History or evidence upon physical/neurological examination of central nervous
system disease (e.g., seizures) unrelated to cancer unless adequately controlled
by medication;

- Acute bacterial or fungal infection requiring intravenous antibiotics within 7
days of enrollment;

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration;

- Patients known to be HIV positive or have active viral hepatitis.