Paclitaxel, Carboplatin and Cetuximab (PCC) With Cetuximab, Docetaxel, Cisplatin and Fluorouracil (C-TPF) in Previously Untreated Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

1. Patients with biopsy-proven squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx.
2. Biopsy material sufficient for HPV status determination available
3. Patients should have stage IV disease, stage T0-4 N2b-2c/3 M0 (for nasopharynx patients, stage N1 is eligible). Measurable disease in either the T or N site by RECIST is required.
4. Patients with stage Tx primary disease are eligible if there is N2b-c/3 lymphadenopathy
5. ECOG PS 0-1
6. Age \>/= 18 years
7. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC \>/= 1500 cells/mm\^3 and platelet count \>/= 100,000 cells/mm\^3; adequate hepatic function with bilirubin \</= ULN (excluding Gilbert's disease), AST and ALT may be up to 2.5 x ULN if alkaline phosphatase is normal. Alkaline phosphatase may be up to 4 x ULN if AST and ALT are normal. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
8. Creatinine clearance \>/=40 ml/min determined by 24 hour collection or nomogram:CrCl male = (140 - age) x (wt in kg)/serum Cr x 72 or CrCl female = 0.85 x (CrCl male)
9. Patients should have no serious acute or chronic co-morbid condition, or acute infection, which in the judgment of the attending physician would affect administration of the induction chemotherapy regimens.
10. Patients must sign a study-specific informed consent form

Exclusion Criteria:

1. Histology other than squamous cell carcinoma
2. Proven distant metastases (below the clavicle) by clinical or radiographic measures
3. ECOG\>1
4. Prior chemotherapy, within the previous 3 years
5. Prior radiotherapy to the head and neck
6. Prior cetuximab therapy or prior therapy with any other drug that targets the EGFR pathway
7. Initial surgical resection rendering the patient clinically and radiologically disease free
8. Simultaneous primary invasive cancers, excluding superficial non-melanoma skin cancers
9. Patients with a history of another malignancy (excluding non melanoma skin cancers, and cancers treated \> 3 years prior for which patient remains continuously disease free
10. Men and women of childbearing potential (WOCBP) unwilling to consent to using effective contraception while on treatment and for at least 3 months thereafter
11. Women who are pregnant or breastfeeding
12. Pre-existing peripheral neuropathy CTCAE Grade 2 or worse
13. Hemoglobin \< 8.0g/dL
14. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80