Clinical trial NCT01419587: Ketogenic Diet With Chemoradiation for Lung Cancer (KETOLUNG)
Official title: A Phase I Trial of a Ketogenic Diet With Concurrent Chemoradiation for Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Carcinoma, Non-Small-Cell Lung
Non small cell lung cancer
NSCLC
Ketogenic Diet
radiotherapy
paclitaxel
carboplatin
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
name: Nutricia North America
First posted: 2011-08-18
Enrollment: 11
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 lung cancer patients.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of Adverse Events (Safety)
timeFrame: Weekly for 8 weeks
Secondary outcomes:
measure: Ketone levels
timeFrame: Daily during treatment for 6 weeks
measure: Blood glucose levels
timeFrame: Daily during treatment for 6 weeks
measure: Oxidative stress parameters
timeFrame: Weeks 1, 2, 3, 4, 5, and 6 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: The Department of Radiation Oncology, The University of Iowa
name: Bryan G. Allen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, Rodman SN III, Snyders TP, Chenard CA, Eichenberger-Gilmore JM, Bodeker KL, Ahmann L, Smith BJ, Vollstedt SA, Brown HA, Hejleh TA, Clamon GH, Berg DJ, Szweda LI, Spitz DR, Buatti JM, Allen BG. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials. Radiat Res. 2017 Jun;187(6):743-754. doi: 10.1667/RR14668.1. Epub 2017 Apr 24.