Ketogenic Diet With Concurrent Chemoradiation for Pancreatic Cancer

Study Overview
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Brief Summary
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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
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Standard treatment for pancreatic 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 pancreatic 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

Official Title
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A Phase I Trial of a Ketogenic Diet With Concurrent Chemoradiation for Pancreatic Cancer.

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Dietary Supplement: Ketogenic diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a cytological or histological diagnosis of adenocarcinoma arising in the pancreas. Adenosquamous cancers will be acceptable. Cancer should be staged via AJCC as IIA, IIB, or III (T3 or T4, any N, M0) 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 < 3.0 mg/dl Hgb A1C < or = to 8% AST(SGOT) < or = 5 X institutional upper limit of normal OR a stable or a decreasing test value in patients who have undergone placement of an intrabiliary stent. Both the treating radiation oncologist and medical oncologist must agree that the potential subject's test value is acceptable for study accrual. 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: Prior abdominal radiotherapy. Prior therapy, with the intent to treat, the current diagnosis of pancreatic cancer. Known G6PD (glucose-6-phosphate dehydrogenase) deficiency. Patients on corticosteroids for any reason. Living alone at time of diet initiation. 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 mellitus 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, psychiatric illness/social situations, or any other condition 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic diet<br>Diet designed to maintain elevated ketone levels during therapy | Dietary Supplement: Ketogenic diet<br>* A ketogenic diet matching the fat to carbohydrate + proteins in Keto-Cal(R) 4:1 by Nutricia North America.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events (Safety) | Categorize and quantify adverse events in subjects implementing a ketogenic diet while undergoing definitive chemoradiation therapy. | Weekly for 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ketone levels | Quantify blood ketone levels via both finger-stick prior to daily radiation therapy and weekly lab analysis while on a ketogenic diet. Radiation is administered Monday through Friday only. | Daily during treatment for 6 weeks | 
| Blood glucose levels | Quantify blood glucose levels via finger-stick prior to daily radiation therapy while on a ketogenic diet. Radiation therapy is administered Monday through Friday only. | Daily during treatment for 6 weeks | 
| Oxidative stress parameters | Determine oxidative stress parameters in plasma and urine samples during the course of treatment. | Weeks 1, 2, 3, 4, 5, and 6 of treatment and at 1 month follow-up | 
| Progression Free Survival (months) | From date of treatment until the first date of documented progression or date of death, whichever comes first, assessed no less than every 12 months for the first 60 months post-therapy. | Every 12 months for 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gemcitabine, Pancreatic neoplasms, Pancreatic cancer, Ketogenic Diet, radiotherapy