Ketogenic Diet With Chemoradiation for Lung Cancer (KETOLUNG)

Standard treatment for lung cancer includes chemotherapy concurrent with radiation therapy
(chemoradiation).

This study is a phase I trial to determine the safety of dietary manipulation during
chemoradiation for lung 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 NSCLC.

- Candidate for primary chemoradiation as decided by both medical and radiation
oncology.

- Cancer should be staged via AJCC as IIIA or IIIB.

- Stage IV patients are considered provided they have a single non-CNS metastasis (that
is amenable to treatment with radiation therapy).

- Age ≥ 18 years

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

- Hypertensive medication should be initiated or increased for optimal blood pressure
control according to standard public health guidelines prior to starting the ketogenic
diet.

- 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 < or = to 8%

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

- creatinine < 1.5 X institutional upper limit of normal OR 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 thoracic radiotherapy.

- Prior therapy, with the intent to treat, the current diagnosis of lung cancer.

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

- Systemic corticosteroids for any reason (inhaled corticosteroids are allowed).

- 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.

Female and male patients of all ethnic groups will be eligible for treatment in these
protocols.