Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer

PRIMARY OBJECTIVES:

I. To assess the cumulative incidence of local/regional failure at 2 years after study
registration.

SECONDARY OBJECTIVES:

I. To characterize the rate of acute grade 3 or higher functional mucosal adverse events (up
to 1 month post-radiation therapy [XRT]) associated with adjuvant docetaxel +
hyperfractionated radiotherapy (key secondary endpoint).

II. To assess changes in overall survival, disease-free survival, distant failure rates, and
quality of life (QOL) associated with adjuvant docetaxel and hyperfractionated radiation.

III. To characterize other acute adverse events (up to 1 month post-XRT) and late grade 3 or
higher non-hematologic adverse events (up to 2 years post-XRT) associated with adjuvant
docetaxel + hyperfractionated radiotherapy.

TERTIARY OBJECTIVES:

I. To determine the genetic alterations of oropharynx tumor specimens and the detection rate
of corresponding cell-free deoxyribonucleic acid (cfDNA) in the pre-surgical, post-surgical,
and post-radiation blood of oropharynx cancer patients.

OUTLINE:

Patients receive docetaxel intravenously (IV) over 1 hour on days 1 and 8 and undergo
hyperfractionated intensity-modulated radiation therapy (IMRT) twice daily (BID) 5 days a
week on days 1-12 for a total of 20 fractions.

After completion of study treatment, patients are followed up at 14 days, 1 month, every 3
months for 2 years, every 6 months for 1 year and then annually for 2 years.

Inclusion Criteria:

- PRE-REGISTRATION

- Provide written informed consent

- Submission of research blood draw to be stored until after surgical resection of the
primary tumor and confirmation of human papilloma virus (HPV) positivity (Mayo Clinic
Rochester patients only)

- Patients with oropharynx carcinoma with a smoking history of ˂ 10 pack-year or
equivalent 10 year history of tobacco product use and no recent history (within last 5
years) of tobacco use

- REGISTRATION

- Histological confirmation of HPV+ squamous cell carcinoma of the oropharynx; HPV
positivity will be defined as positive staining for p16 on immunohistochemistry (IHC)

- Gross total surgical resection with curative intent of the primary tumor and at least
unilateral neck dissection within 7 weeks of registration

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Smoking history < 10 pack years or equivalent 10 year history of tobacco product use

- Absence of distant metastases on standard diagnostic work-up =< 10 weeks prior to
registration; (chest computed tomography [CT], chest x-ray [CXR], positron emission
tomography [PET]/CT, etc.)

- Must have one of the following risk factors:

- Lymph node > 3 cm

- 2 or more positive lymph nodes

- Perineural invasion

- Lymphovascular space invasion

- T3 or microscopic T4a primary disease

- Lymph node extracapsular extension

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dL

- Direct bilirubin within upper limit of normal (ULN)

- Creatinine =< ULN x 1.5

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Ability to complete questionnaire(s) by themselves or with assistance

- Provide informed written consent

- Willingness to return to enrolling institution for follow-up (during the active
monitoring phase of the study)

Exclusion Criteria:

- Any significant tobacco history within the past five years

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
positive

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic
skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior
malignancy, they must not be receiving other specific treatment for their cancer

- History of myocardial infarction =< 180 days prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias

- Prior history of radiation therapy to the affected site

- History of connective tissue disorders such as rheumatoid arthritis, lupus, or
Sjogren's disease

- Presence of any of the following risk factors after surgery:

- Any positive surgical margin

- Adenopathy below the clavicles

- Prior systemic chemotherapy for the study cancer; NOTE: prior chemotherapy for a
different cancer is allowable

- History of allergic reaction to docetaxel

- Receiving any medications or substances that are strong or moderate inhibitors of
cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

- Use of strong or moderate inhibitors is prohibited =< 7 days prior to
registration

- Receiving any medications or substances that are inducers of CYP3A4

- Use of inducers is prohibited =< 12 days prior to registration