Ketogenic Diet With Concurrent Chemoradiation for Pancreatic Cancer (KETOPAN)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Dietary supplement: Ketogenic diet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Holden Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Nutricia North America
• Investigators: Principal Investigator: Bryan G. Allen, MD, PhD, The Department of Radiation Oncology, The University of Iowa

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimate): August 18, 2011

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: January 4, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: radiotherapy; gemcitabine; Pancreatic cancer; Ketogenic Diet; Pancreatic neoplasms
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 201102772; 1R21CA161182 (U.S. NIH Grant/Contract)