Safety and Efficacy Study of P276-00 in Combination With Radiation in Subjects With Advanced Head and Neck Cancer (SPARK)

Inclusion Criteria:

1. Disease specifications:

   • Phase I component: Radiation naïve subjects with histologically and/ or cytologically confirmed squamous cell carcinoma of head and neck that is non-metastatic, unresectable and recurrent. Radiation naïve subjects with non-recurrent, non-metastatic, unresectable, disease can also be enrolled if he/she is intolerant to and/or unwilling for chemoradiotherapy involving standard cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU, taxanes, methotrexate, etc)
   • Phase II component: Radiation naïve subjects with non-recurrent, non-metastatic, unresectable, locally advanced squamous cell carcinoma of head and neck who are intolerant to and/or unwilling for chemoradiotherapy involving standard cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU, taxanes, methotrexate, etc).

2. Treatment specifications:

   • Phase I Component: subjects must not have received any treatment (chemotherapy, targeted or biologic agents, radiotherapy, surgery etc) for the recurrent disease.
   • Phase II Component: The subjects must not have been curatively operated for the disease.
3. Subjects must have completed any prior chemotherapy, biologic/targeted anti-cancer therapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin C) before initiation of protocol treatment and subjects must have recovered (to < or = grade 1) from the toxic effects from any prior therapy
4. Measurable disease as per RECIST criteria.
5. Age > or = 18 years
6. ECOG (Eastern Cooperative Oncology Group) performance status < or = 2
7. Life expectancy of at least 12 weeks

8. Normal organ and marrow function:

   • Hemoglobin > or = 100 g/L
   • Leukocytes > or = 3 x 109/L
   • Absolute Neutrophil Count (ANC)> or = 1.5 x 109/L
   • Platelets > or = 75 x 109/L
   • Total bilirubin < or = 1.5 X institutional Upper Limit of Normal (ULN)
   • AST(SGOT)< or = 2.5 X institutional ULN
   • ALT(SGPT)< or = 2.5 X institutional ULN
   • Creatinine < or = 1.5 X institutional ULN
9. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Nasopharyngeal carcinoma
2. Subjects who had received any other investigational drug within 1 month prior to day 1 of study drug administration or who have not recovered (to < or = grade 1) from adverse effects of the investigational agent received prior to this period.
3. History of unstable angina or myocardial infarction or stroke within 6 months prior to initiation of protocol treatment.
4. QTcF > 450 msec
5. Subjects with uncontrolled inter-current illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, psychiatric illness or any condition that would limit compliance with study requirements.
6. Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B.
7. Women who are pregnant or lactating.
8. Women of childbearing potential [defined as a sexually mature woman who has not undergone hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e. who has had menses any time in the preceding 24 consecutive months)] and men, not agreeing to use at least two approved methods of contraception, including at least one barrier method prior to study entry (after signing the informed consent document), during the duration of study participation and for at least 4 weeks after withdrawal from the study drug, unless they are surgically sterilised.
9. Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at an unacceptable risk or deems the subject not suitable for participation in the study.