De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca

The aim is to evaluate the pathological response rate of HPV positive and/or p16 positive
low-risk oropharyngeal squamous cell carcinoma (OPSCC) after de-intensified chemoradiotherapy
(CRT). Patients will receive 54 to 60 Gy of Intensity Modulated Radiotherapy (IMRT) with
concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) will
be obtained 4 to 8 weeks after completion of CRT to assess response. All patients will have
surgical resection of any clinically apparent residual primary tumor or biopsy of the primary
site if there is no evidence of residual tumor and will undergo a limited neck dissection to
encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after
CRT. The primary endpoint of this study is the rate of pathological complete response (pCR)
after CRT. Longitudinal assessments of quality of life and patient reported outcomes will be
obtained prior to, during, and after CRT.

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. The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

8. Complete Blood Count (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 upper
limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase
(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.