De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

The proposed study is a follow-up study to NCT01530997. In NCT01530997, patients with HPV
positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) received
de-intensified chemoradiotherapy (CRT) followed by a limited surgical evaluation. The primary
endpoint of NCT01530997 was the rate of pathological complete response (pCR) after CRT. Power
computations were performed for N=40 and were based on the null hypothesis (H0) that the pCR
for de-intensified chemoradiotherapy is at least 87%, the historical rate. The type 1 error
for this calculation was 14.2%. 43 patients enrolled and 38 were evaluable for the primary
endpoint. The observed pCR rate was 89% (34/38). Since the observed pCR rate was excellent in
NCT01530997 and was in concordance with the expected rate, in the proposed study we will not
mandate a post-CRT surgical evaluation. Instead a PET/CT 10 to 16 weeks post-CRT will be used
to determine whether a surgical evaluation is needed.

Inclusion Criteria:

1. ≥ 18 years of age (no upper age limit)

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 ≤ 30 pack-years smoking history WITH ≥ 5 years
abstinence from smoking

5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
prior to treatment

6. ECOG Performance Status 0-1

7. CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow
function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl.

8. 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.

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

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

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

12. 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. Unresectable disease (e.g. immobile node on physical exam, nodal disease that
radiographgically involves the carotid arteries, nerves)

4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)

5. 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; Systemic lupus; Psoriatic arthritis.

6. Known HIV positive.