Inclusion Criteria:

Inclusion Criteria:

Treatment Group 1 (Cohorts 1 & 2) - Radiation and Sorafenib Only.

1. Previously untreated squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx, or larynx. Histological or cytological confirmation is required. The
disease must be considered to be potentially curable with radiation only.

2. Stage III or IV disease (UICC/AJCC classification, 6th edition)

3. Age ≥18

4. Patients for whom concurrent cisplatinum is contraindicated due to poor patient
tolerance (significant weight loss > 10% of body weight, mild renal dysfunction,
ototoxicity, neuropathy, or age >70) yet deemed fit for radical radiation.

5. Signed written consent.

6. Availability for follow-up after treatment.

7. If the patient is fertile he/she is aware of the risk of becoming pregnant or
fathering children and will use adequate contraception (oral contraception, IUD,
diaphragm and spermicide or male condom and spermicide) throughout therapy and for at
least 2 weeks after therapy.

8. Life expectancy greater than 6 months

Inclusion Criteria:

Treatment group 2 (Cohorts 3 to 5) - Radiation, Sorafenib and
Cisplatin.

1. Previously untreated squamous cell carcinoma of the oral cavity, oropharynx,
hypopharynx, or larynx. Histological or cytological confirmation is required. The
disease must be considered to be potentially curable by combined chemoradiation.

2. Stage III or IV disease (UICC/AJCC classification, 6th edition)

3. Age ≥18.

4. Signed written consent.

5. Availability for follow-up after treatment.

6. If the patient is fertile, he/she is aware of the risk of becoming pregnant or
fathering children and will use adequate contraception (oral contraception, IUD,
diaphragm and spermicide or male condom and spermicide) throughout therapy and for at
least 3 months after therapy.

7. Life expectancy greater than 6 months

Exclusion Criteria:

Treatment Group 1 (Cohorts 1 & 2) - Radiation and Sorafenib Only.

1. ECOG performance status 3 or 4

2. Absolute neutrophil count <1.0 X 109/L, platelet count <100 X 109/L or hemoglobin <90
g/L.

3. Serum bilirubin ≥1.5 times ULN or AST/ALT ≥ 2.5 times ULN.

4. Calculated creatinine clearance (Cockcroft-Gault) <40 mL/min. For patients in whom
the calculated creatinine clearance is borderline, GFR may be estimated by nuclear
renogram with the creatinine clearance ≥ 40 mL/min to be eligible.

5. Uncontrolled hypertension despite adequate anti-hypertensive medications

6. Bleeding diathesis

7. Significant inter-current illness that will interfere with the radiation therapy
during the trial such as HIV infection, pulmonary compromise, active significant
alcohol abuse, active infection or febrile illness

8. Any history of myocardial infarction, congestive heart failure (NY Heart Association
Class 3 or 4), any history of ventricular arrhythmias, angina or active coronary
heart disease within 6 months.

9. Primary cancers of the nasal and paranasal cavities, and of the nasopharynx.

10. Evidence of distant metastases. If based on the best available clinical evidence the
investigator wishes to enroll the subject on trial, discussion and documentation with
one of the principal investigators is required.

11. Weight loss greater than 25% of usual body weight in the 3 months preceding trial
entry.

12. High risk for poor compliance with therapy or follow-up as assessed by investigator.

13. Pregnant or lactating women.

14. Prior radiation therapy to greater than 30% of the bone marrow

15. Prior experimental therapy for cancer within 30 days of entering the trial.

16. Prior radiation for head and neck cancer.

17. Patients with prior cancers, except: those diagnosed more than five years ago with no
evidence of disease recurrence and a clinical expectation of recurrence of less than
5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the
cervix. However, any patient with previous invasive breast cancer, prostate cancer or
melanoma is excluded.

Exclusion Criteria: Treatment group 2 (Cohorts 3 to 5) - Radiation, Sorafenib and
Cisplatin.

1. ECOG performance status 3 or 4

2. Absolute neutrophil count <1.0 X 109/L, platelet count <100 X 109/L or hemoglobin <90
g/L.

3. Serum bilirubin ≥1.5 times ULN or AST/ALT ≥ 2.5 times ULN.

4. Calculated creatinine clearance (Cockcroft-Gault) <55 mL/min. For patients in whom
the calculated creatinine clearance is borderline, GFR may be estimated by nuclear
renogram with the creatinine clearance ≥ 55 mL/min to be eligible.

5. Uncontrolled hypertension despite adequate anti-hypertensive medications

6. Bleeding diathesis

7. Significant inter-current illness that will interfere with the chemotherapy or
radiation therapy during the trial such as HIV infection, cardiac insufficiency,
pulmonary compromise, active significant alcohol abuse, active infection or febrile
illness,

8. Any history of myocardial infarction, any history of ventricular arrhythmias, angina
or active coronary heart disease within 6 months. Significant cardiac disease
resulting in an inability to tolerate the intravenous fluid load as required for
administration of cisplatin.

9. Primary cancers of the nasal and paranasal cavities, and of the nasopharynx.

10. Evidence of distant metastases. If based on the best available clinical evidence the
investigator wishes to enroll the subject on trial, discussion and documentation with
one of the principal investigators is required.

11. Symptomatic peripheral neuropathy ≥ grade 2.

12. Clinically significant sensori-neural hearing impairment which may be exacerbated by
cisplatin (audiometric abnormalities without corresponding clinical hearing
impairment will not be grounds for exclusion)

13. Weight loss greater than 20% of usual body weight in the 3 months preceding trial
entry.

14. High risk for poor compliance with therapy or follow-up as assessed by investigator.

15. Pregnant or lactating women.

16. Prior radiation therapy to greater than 30% of the bone marrow

17. Prior experimental therapy for cancer within 30 days of entering the trial.

18. Prior radiation for head and neck cancer.

19. Patients with prior cancers, except: those diagnosed more than five years ago with no
evidence of disease recurrence and a clinical expectation of recurrence of less than
5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the
cervix. However, any patient with previous invasive breast cancer, prostate cancer or
melanoma is excluded.