Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

This is a non-randomized, open-label phase II trial of 40 patients with poor prognosis head
and neck cancer, defined as surgically unresectable and/or ≥N2b disease and judged
appropriate for non-surgical definitive therapy. Patients must have Eastern Cooperative
Oncology Group (ECOG) performance status of 0-1 with good organ function and will be treated
with six weekly cycles of carboplatin, nab-paclitaxel and cetuximab prior to scheduled
concomitant chemoradiation. The study is designed to evaluate whether this induction regimen
can result in an improved response rate (complete response (CR) + partial response (PR)) with
less toxicity than the current standard induction docetaxel, cisplatin and 5-fluorouracil
(TPF) regimen.

Inclusion Criteria:

- Histologically or cytologically confirmed SCCHN or poorly differentiated or
undifferentiated cancer of the head and neck.

- Measurable disease.

- All primary sites are eligible excluding nasopharyngeal.

- Surgically unresectable and/or N2b or greater nodal disease; Note: surgical
unresectability will be defined as the combination of the treating surgeon's judgment
of unresectability plus one of the following objective criteria:

- Encasement of tumor or nodes to the carotid artery or ¾ encasement of the carotid
artery.

- Involvement of prevertebral musculature

- Invasion of the bone of the skull base

- Need for glossectomy or extensive glossal resection where functional outcome is
considered unacceptable to surgeon or patient

- Involvement of the cervical spine

- Severe, unacceptable functional deficit that would result from any proposed
definitive surgical resection.

- ECOG performance status 0-1

- Prior therapy:

- Chemotherapy: No prior chemotherapy for the treatment of SCCHN.

- Platinum chemotherapy: No previous history of carboplatin or cisplatin therapy.

- Nab-paclitaxel: No previous treatment with nab-paclitaxel or another taxane.

- Cetuximab: No previous treatment with cetuximab Or another epidermal growth
factor receptor (EGFR) inhibitor.

- Radiation therapy: No prior radiation to the head and neck region.

- Age > or = 18 years. Men and women are eligible for participation.

- Must have acceptable organ and marrow function as defined below. Laboratory tests
should be completed within 14 days prior to registration:

- Absolute Neutrophil Count (ANC) > or = 1,500/mm3

- Platelets > or = 100,000/mm3

- Hemoglobin (Hgb) > 9g/dL

- Total bilirubin < or = 1.5mg/dL

- Albumin > 2.5 g/dL

- Aspartate aminotransferase (AST)/Alanine Aminotransferase (ALT) < or = 2.5 times
institutional upper limit of normal, alkaline phosphatase < 2.5 x upper limit of
normal, glomerular filtration rate (GFR) > 30 mL/min (by standard Cockcroft and
Gault formula or measured via 24 hour urine collection)

- No pre-existing neuropathy greater than grade I

- Women of childbearing potential must have a negative serum or urine pregnancy test
performed within 7 days prior to day 1 of study treatment.

- Women of childbearing potential and men must agree to use adequate contraception prior
to study entry, for the duration of study participation and for three months after
completing treatment. Adequate contraception is defined as any medically recommended
method (or combination of methods) as per standard of care.

- Patients must have the ability to understand and the willingness to sign a written
informed consent document.

- Patients must have a negative result for preformed immunoglobulin E (IgE) antibodies
to galactose-alpha-1,3,-galactose.

Exclusion Criteria:

- Prior treatment with any of the study medications.

- Prior radiation to any of the field required to treat the tumor.

- Any metastatic disease.

- The patient may have had a prior malignancy but must be disease-free for three years
prior to study entry. A history of superficial non-melanoma skin cancer or in situ
carcinoma of the cervix less than three years will be allowed.

- Pregnant or lactating female

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring IV antibiotics, or psychiatric illness/social situations that
would limit compliance with study requirements. Cardiac disease such as symptomatic
congestive heart failure, unstable angina pectoris, or myocardial infarction will
result in exclusion only if active within the past six months. Cardiac dysrhythmia
will only result in exclusion if active and symptomatic (for example, rate-controlled
atrial fibrillation will not result in exclusion).