A Clinical Study to Assess Radiation Induced Mucositis in Subjects with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

A Multicenter, Phase II/III Study to Assess Radiation Induced Mucositis in Subjects with Locally Advanced Squamous Cell Carcinoma of the Head and Neck Administered Cisplatin and Radiation with or without P276-00

The Phase II component will be a single arm, open label, multicenter study to assess RIM in subjects with locally advanced SCCHN treated with P276-00 in combination with radiation therapy and cisplatin. '

The Phase III component will be a randomized, assessor blinded, multicenter, two-arm study to compare the time to onset of WHO Grade ≥ 3 RIM in subjects with locally advanced SCCHN (OC, OP, HP, and L) who are receiving definitive CRT for treatment of their malignancy. Subjects receiving definitive CRT will receive weekly intravenous cisplatin administered during radiation.

Inclusion Criteria:

1. Able to understand and willing to give an informed consent for the study.

2. Pathologically (histologically or cytologically) confirmed (from primary tumor and/or lymph nodes), non-metastatic diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx eligible for treatment with concomitant chemoradiation as first-line treatment; subjects with a history of surgical management are not eligible

3. Have a plan to receive a continuous course of radiation (3DRT or IMRT) as single daily fractions of 2.0 Gy, with a cumulative radiation dose between 66 and 70 Gy. Planned radiation treatment fields must include at least 2 oral sites (maxillary or mandibular labial mucosa, right or left buccal mucosa, right or left floor of the mouth, ventral tongue, right or left lateral tongue, or soft palate), with each site receiving more than equal to 50 Gy

4. Have a plan to receive a standard cisplatin regimen administered weekly (30 to 40 mg/m2)

5. Have an Eastern Co-operative Oncology Group (ECOG) performance status less than equal to 2

6. Males or females aged 18 years or older

7. Pre-treatment dental procedures must be completed with recovery and the prophylactic insertion of gastric feeding tubes (if planned) prior to entry into the study

8. Adequate bone marrow function measured within two weeks prior to enrollment based upon CBC/differential, defined as follows:

   1. Absolute neutrophil count (ANC) more than equal to 1,500 cells/mm3
   2. Platelets more than equal to 100,000 cells/mm3
   3. Hemoglobin (Hb) more than equal to 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hb more than equal to 8.0 g/dl prior to the start of RT is acceptable)

9. Adequate hepatic function measured within two weeks prior to enrollment defined as follows

   1. Bilirubin less than equal to 1.5 mg/dl
   2. AST less than equal to 2 times ULN
   3. ALT less than equal to 2 times ULN

10. Adequate renal function measured within two weeks prior to enrollment and defined as follows

    1. Serum creatinine less than equal to 1.5 mg/dl
    2. Creatinine clearance (CC) more than equal to 60 ml/min determined by 24-hour urine collection or estimated by the Cockcroft-Gault formula:

11. Have a negative serum pregnancy test for women of childbearing potential at time of screening and negative urine pregnancy test within 72 hrs prior to first dose of study drug

Exclusion Criteria:

1. Tumor of the lips, sinuses, salivary glands, nasopharynx, or unknown primary tumor

2. Metastatic disease (M1) Stage IVC as per the AJCC, 7th edition

3. Prior radiation to the head and neck

4. Have undergone induction CT

5. History of malignant tumors other than HNC (except non-melanoma skin cancer) unless disease free for a minimum of 3 years

6. Severe co-morbidity, defined as:

   1. Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV
   2. Acute myocardial infarction within the last 6 months
   3. Acute bacterial or fungal infection requiring systemic antibiotics at the time of enrollment
   4. Subjects known to be seropositive for human immunodeficiency virus (HIV) or subjects with Acquired Immune Deficiency Syndrome (AIDS), known current acute or chronic Hepatitis B, known Hepatitis C (antigen positive), or hepatic cirrhosis
   5. Subjects with active tuberculosis
   6. Collagen vascular disease, such as scleroderma, as this is thought to predispose subjects to increased risk for radiation-associated toxicities

7. Have used any other investigational drug therapy within 1 month prior to Day 1 of study drug administration or non-recovery (to Grade less than equal to 1) from adverse effects of the investigational agent received prior to this period

8. Prior allergic reaction to any of the agents administered during the course of treatment

9. Have QTcF more than equal to 450 msec at screening

10. Pregnant or breastfeeding women