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

The purpose of this research study is to learn about the effectiveness of using lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck. The cure rate for this type of cancer is estimated to be high, \> 90%. The standard treatment for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is performed afterwards. This standard regimen causes a lot of side effects and long term complications. This study is evaluating whether a lower dose of radiation and chemotherapy may provide a similar cure rate as the longer, more intensive standard regimen. Patients in this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy.

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.

Eligibility Criteria:
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 radiographically 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.