Clinical trial NCT01419483: Ketogenic Diet With Concurrent Chemoradiation for Pancreatic Cancer
Official title: A Phase I Trial of a Ketogenic Diet With Concurrent Chemoradiation for Pancreatic Cancer.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Pancreatic Neoplasms
Keywords: Pancreatic neoplasms
Pancreatic cancer
Ketogenic Diet
radiotherapy
gemcitabine
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: 5
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 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

Eligibility criteria: 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.

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.