Docetaxel and Radiation Therapy in Treating Patients With HPV Positive Oropharynx Cancer

PRIMARY OBJECTIVES:

I. To compare the rates and severity of late grade 3-5 toxicities and percutaneous endoscopic
gastrostomy (PEG) tube dependence between de-escalated adjuvant radiation therapy (DART) and
standard adjuvant therapy.

SECONDARY OBJECTIVES:

I. To assess the cumulative incidence of local/regional failure at 2 years after study
registration for patients treated with DART versus (vs) standard therapy.

II. To compare overall survival, disease-free survival, and distant failure associated with
DART vs standard treatment.

III. To compare the overall quality of life (QOL) between DART and standard adjuvant therapy
at 1-year post-treatment as measured by Functional Assessment of Cancer Therapy (FACT) Head
and Neck (H&N) and European Organization for Research and Treatment of Cancer (EORTC) H&N
quality of life questionnaire (QLQ) 35.

TERTIARY OBJECTIVES:

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

II. To investigate the usefulness of immunologic biomarkers in predicting progression free
survival.

III. To establish a patient derived xenograft panel from representative oropharynx patients.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (DART): Patients undergo 20 fractions of intensity-modulated radiation therapy (IMRT)
or image-guided radiation therapy (IGRT) twice daily (BID) on days 1-12 (Monday - Friday),
and receive docetaxel intravenously (IV) over 1 hour on days 1 and 8 in the absence of
disease progression or unacceptable toxicity.

ARM II (STANDARD OF CARE): Patients undergo 30 fractions of IMRT or IGRT daily on days 1-40
(Monday - Friday), and receive cisplatin IV weekly around days 1, 8, 15, 22, 29 and 36 in the
absence of disease progression or unacceptable toxicity.

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

Inclusion Criteria:

- PRE-REGISTRATION (OPTIONAL)

- Provide written informed consent

- Submission of research blood draw and/or tumor sample

- REGISTRATION

- Histological confirmation of human papillomavirus (HPV) positive (+) 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

- Absence of distant metastases on standard diagnostic work-up =< 16 weeks prior to
registration; (chest computed tomography [CT], chest x-ray [CXR], or positron emission
tomography [PET]/CT)

- 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 primary disease

- Lymph node extracapsular extension

- Obtained =< 35 days prior to registration: absolute neutrophil count (ANC) >=
1500/mm^3

- Obtained =< 35 days prior to registration: platelet count >= 100,000/mm^3

- Obtained =< 35 days prior to registration: hemoglobin >= 8.0g/dL

- Obtained =< 35 days prior to registration: creatinine =< 1.5 mg/dL or creatinine
clearance >= 50 mL/min

- Obtained =< 35 days prior to registration: total or direct bilirubin < 2 x
institutional upper limit of normal (ULN)

- Obtained =< 35 days prior to registration: aspartate aminotransferase (AST) (serum
glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum
glutamate pyruvate transaminase [SGPT]) < 3 x institutional ULN

- 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 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

- 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

- History of allergic reaction to docetaxel

- Receiving any medications or substances which in the opinion of the investigators
would interfere with treatment; examples could include strong inhibitors of CYP3A4 at
oncologist discretion

- Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the
investigator, preclude the use of cisplatin chemotherapy

- If there are 3 or more attempts by the surgeon to clear margins, patient is not
eligible for study