P53 Mutational Status and cf HPV DNA for the Management of HPV-associated OPSCC
P53 Mutational Status and cf HPV DNA for the Management of HPV-associated OPSCC
The primary objective of this study is to evaluate whether genomic based risk-stratification
 can be used in deciding whether to de-intensify in patients with Human Papillomavirus
 (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) with > 10 pack years smoking
 history. Hypothesis: Patients with HPV-associated OPSCC, > 10 pack years smoking history, and
 non-mutated p53 will have similar 2 year progression-free survival (PFS) as patients with <
 10 pack years smoking history.
The proposed study is a follow-up study to LCCC 1120 and 1413. The investigators have shown
 that de-intensification is efficacious in these two phase II studies. A major question is
 whether the investigators can de-intensify in patients with HPV-associated oropharyngeal
 cancer who have smoking histories. The investigators' hypothesis is that genomic profiling of
 patients' tumors (specifically for p53 mutations) will help in triaging patients to
 de-intensification versus standard of care. Patients with HPV-associated OPSCC will be
 enrolled regardless of smoking history and p53 mutational status will be assessed in patients
 with a smoking history. The investigators will use the same de-intensification
 chemoradiotherapy regimen already evaluated in LCCC 1120 and 1413 in patients with
 HPV-associated OPSCC who have a minimal smoking history and in patients with a smoking
 history but with wild-type p53. Patients with a smoking history who have mutated p53 will not
 receive de-intensified chemoradiotherapy, but instead will receive standard doses. The
 hypothesis is that by using genomics in the patients with a significant smoking history, the
 investigators will better select those who can be safely de-intensified. Circulating free HPV
 DNA (cf-HPV-DNA) will also be prospectively assessed from blood samples.
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. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
 prior to treatment

 5. ECOG Performance Status 0-1

 6. 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

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

 8. Negative pregnancy test within 2 weeks prior to treatment for women of childbearing
 potential

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

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

 11. 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.