HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer

Inclusion Criteria:

Inclusion criteria will be the same for Phase I and Phase II.

1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx status post gross total resection with pathology showing one or more of the following intermediate risk factors: T3/4 disease, positive lymph node(s), close margin(s), perineural invasion, and/or lymphovascular invasion

2. Age ≥18 years

3. ECOG performance status 0-2

4. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

5. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.

6. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

Phase I:

1. Distant metastasis

2. Stage I and II glottic squamous cell carcinoma

3. High risk factors following surgical resection requiring concurrent chemotherapy: positive margin(s) and/or extranodal extension

4. Feeding tube dependence at baseline assessment.

5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer. For thyroid cancer, surgery may occur before or after treatment, provided all other eligibility criteria are met.

6. Prior invasive malignancy with an expected disease-free interval of less than 3 years

7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields

8. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.

9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements

10. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

11. History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant

Phase II:

The exclusion criteria will be the same as Phase I except for feeding tube dependence. Patients who are feeding tube dependent are excluded from Phase I to accurately assess treatment associated toxicity affecting swallowing and oral intake. During Phase II, patients who are feeding tube dependent will be eligible to enroll and stratified at randomization.