Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma

Inclusion Criteria:

1. ≥ 18 years of age

2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx

3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive

4. ≤ 10 pack-years smoking history or > 5 years of abstinence from smoking

5. History/physical examination within 8 weeks prior to registration

6. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
prior to registration.

7. ECOG Performance Status 0-1

8. CBC/differential obtained within 4 weeks prior to registration, with adequate bone
marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,800
cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl.

9. Adequate renal and hepatic function within 4 weeks prior to registration, defined as
follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN;
AST or ALT < 3 x the institutional ULN.

10. Negative serum pregnancy test within 2 weeks prior to registration for women of
childbearing potential.

11. Women of childbearing potential and male participants who are sexually active must
practice adequate contraception during treatment and for 6 weeks following treatment.

12. Patients must be deemed able to comply with the treatment plan and follow-up
schedule.

13. Patients must provide study specific informed consent prior to study entry.

Exclusion Criteria:

1. Prior history of radiation therapy to the head and neck

2. Prior history of head and neck cancer.

3. Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive
heart failure requiring hospitalization within the last 6 months; Transmural
myocardial infarction within the last 6 months; Acute bacterial or fungal infection
requiring intravenous antibiotics at the time of registration; Chronic Obstructive
Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
or precluding study therapy at the time of registration; Hepatic insufficiency
resulting in clinical jaundice and/or coagulation defects; Note, however, coagulation
parameters are not required for entry into this protocol; Pre-existing ≥ grade 2
neuropathy; Prior organ transplant.

4. Known HIV positive

5. Significant pre-existing hearing loss, as defined by the patient or treating
physician.