Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

PRIMARY OBJECTIVES:

I. To determine the progression-free survival at 2 years in patients with HPV-positive head
and neck squamous cell carcinoma (HNSCC) who receive induction chemotherapy followed by dose
de-intensified chemoradiotherapy.

SECONDARY OBJECTIVES:

I. To determine the overall survival and local-regional control for patients with
HPV-positive HNSCC who receive induction chemotherapy and dose de-intensified
chemoradiotherapy.

II. To determine the incidence of acute grade 3+ mucosal and esophageal toxicity associated
with attenuated concurrent chemoradiotherapy in patients with HPV-positive HNSCC.

III. To determine the incidence of late toxicity in patients with HPV-positive HNSCC who
receive the dose de-intensified chemoradiotherapy.

IV. To estimate the incidence of all toxicity (hematologic and non-hematologic) associated
with protocol treatment for all patients on trial.

V. To estimate the response rate of HPV-positive to induction chemotherapy using carboplatin
and paclitaxel.

VI. To determine the effect of reduced radiation dose on short-term and long-term quality of
life among patients treated by chemoradiotherapy.

OUTLINE:

INDUCTION: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV
over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of
disease progression or unacceptable toxicity.

CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients
receive paclitaxel IV over 1 hour weekly and undergo intensity-modulated radiation therapy
(IMRT) daily 5 days a week for 5.5 weeks in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 3
months for 1 year, and then every 6 months for 2 years.

Inclusion Criteria:

- Pathologically (histologically or cytologically) proven (from primary lesion and/or
lymph nodes) diagnosis of HPV-positive squamous cell carcinoma of the oropharynx,
hypopharynx, or larynx; HPV-positivity will be defined as tumors that are p16-positive
by immunohistochemistry

- Clinical stage III or IV disease; note: patients with M1 tumors are not eligible

- Appropriate stage for protocol entry, including no distant metastases, based upon the
following minimum diagnostic workup:

- History/physical examination within 4 weeks prior to registration, including
assessment of weight loss in past 6 months

- Chest x-ray (or chest computed tomography [CT] scan or positron emission
tomography [PET]/CT scan) within 6 weeks prior to registration

- CT scan or magnetic resonance imaging (MRI) of the head and neck (of the primary tumor
and neck nodes) and PET/CT scan

- Zubrod performance status 0-1

- Absolute neutrophil count (ANC) > 1,800 cells/mm^3

- Platelets > 100,000 cells/mm^3

- Hemoglobin (Hgb) > 8.0 g/dl (note: the use of transfusion or other intervention to
achieve Hgb > 8.0 g/dl is acceptable)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper
limit of normal

- Serum creatinine =< 1.5 mg/dl or institutional upper limit of normal

- Creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated
by Cockcroft-Gault formula

- Negative serum pregnancy test within 7 days prior to start of induction chemotherapy
(ICT) for women of childbearing potential

- Women of childbearing potential and male participants are counseled on birth control
and must agree to use a medically effective means of birth control throughout their
participation in the treatment phase of the study (until at least 60 days following
the last study treatment)

- Patient must sign study specific informed consent prior to study entry

Exclusion Criteria:

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years

- Patients with simultaneous primaries or bilateral tumors are excluded

- Patients who have had initial surgical treatment other than the diagnostic biopsy of
the primary site or nodal sampling of the neck disease are excluded

- Patients with unknown primary tumor sites are excluded

- Patients who present with a cervical lymph node metastasis of unknown primary origin

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable

- Prior radiotherapy that would result in overlap of radiation therapy fields

- Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or
salivary glands

- Recurrent head and neck cancer

- Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable
angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive
heart failure, and cardiomyopathy with decreased ejection fraction

- Congestive heart failure with left ventricular ejection fraction < 20%

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

- Active lupus erythematosus or scleroderma with ongoing physical manifestations

- Any uncontrolled condition, which in the opinion of the investigator, would interfere
in the safe and timely completion of study procedures

- Pregnant or lactating women or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception

- Prior allergic reaction to the study drug(s) involved in this protocol

- Patient is enrolled in another investigational trial