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