Clinical trial NCT01975766: Ketogenic Diet Phase 1 for Head & Neck Cancer
Official title: A Phase I Trial of a Ketogenic Diet With Concurrent Chemoradiation for Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Head and Neck Neoplasms
Keywords: Carcinoma, squamous cell of head and neck
Head and neck cancer
ketogenic diet
radiotherapy
cisplatin
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
name: Nutricia North America
name: Holden Comprehensive Cancer Center
First posted: 2013-11-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study investigates if using a very low carbohydrate diet during combined chemotherapy and radiation therapy is safe and if it can be tolerated by patients.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of adverse events (safety)
timeFrame: weekly for 5 weeks
Secondary outcomes:
measure: Ketone levels
timeFrame: Daily during treatment for 5 weeks
measure: Blood glucose levels
timeFrame: daily during treatment for 5 weeks
measure: Oxidative stress parameters
timeFrame: Weeks 1, 2, 3, 4, and 5 of treatment and at 1 month follow-up
measure: Progression Free Survival (months)
timeFrame: Every 12 months for 60 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: University of Iowa
name: Bryan G. Allen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Allen BG, Bhatia SK, Buatti JM, Brandt KE, Lindholm KE, Button AM, Szweda LI, Smith BJ, Spitz DR, Fath MA. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clin Cancer Res. 2013 Jul 15;19(14):3905-13. doi: 10.1158/1078-0432.CCR-12-0287. Epub 2013 Jun 6.