Ketogenic Diet Phase 1 for Head & Neck Cancer

Standard treatment for head & neck cancer often includes chemotherapy concurrent with
radiation therapy (chemoradiation).

This study is a phase I trial to determine the safety of dietary manipulation during
chemoradiation for head & neck cancer. Specifically, pre-clinical data from mouse studies
indicates a ketogenic diet increases tumor cell killing.

Participants will:

- Utilize a specialized ketogenic diet designed by bionutritional services of the clinical
research unit. This diet begins 2 days before chemoradiation and continues through at
least 5 weeks of chemoradiation.

- Have blood drawn for research purposes weekly to determine measurements of oxidative
stress

- Have urine collected sporadically through the study to determine measurements of
oxidative stress

- Keep a diary of concomitant medications, side effects, and blood sugars

- Have follow-up to monitor for outcomes and overall survival

Inclusion Criteria:

- Histologically or cytologically documented squamous cell carcinoma of the oropharynx,
larynx or hypopharynx. HPV status will not be assessed for eligibility; while HPV
status may affect response to therapy, efficacy is not an outcome measure for this
phase I study.

- Candidate for primary chemoradiation as decided by an interdisciplinary team including
otolaryngology, medical oncology, and radiation oncology.

- Cancer should be staged via AJCC as stage II, III or IVa.

- Age ≥ 18 years

- ECOG performance status 0-2 (Karnofsky > 50%, see Appendix A).

- Patients must have normal organ and marrow function as defined below:

- leukocytes ≥ 3,000/mm3

- absolute neutrophil count ≥ 1,500/mm3

- platelets ≥ 100,000/mm3

- total bilirubin < 1.5 mg/dl

- Hgb A1C < 8%

- AST(SGOT) < 2 X institutional upper limit of normal

- creatinine < 1.5 X institutional upper limit of normal OR calculated creatinine
clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional
normal.

- Not pregnant. 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 and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.

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

Exclusion Criteria:

- Life expectancy of 3 or less months.

- Prior neck and/or upper thoracic radiotherapy that would cause an overlap of treatment
fields.

- Prior therapy to the head and neck, with the intent to treat, the current diagnosis of
head & neck cancer.

- Known / established G6PD (glucose-6-phosphate dehydrogenase) deficiency.

- Chronic system corticosteroids for any reason (inhaled corticosteroids are allowed).
Pre-medication for chemotherapy is acceptable.

- Other investigational agents/therapy with the intention to treat the disease under
study (observational or imaging trials are acceptable).

- Uncontrolled diabetes defined as a hemoglobin A1C level > 8% (therapeutic action is
indicated at greater than 8%).

- Diabetes is not exclusionary provided the patient is not maintained with either oral
medications or insulin.

- 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 would limit compliance with
study requirements as determined by study team members.

- Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are
well documented.