Strict Classic Ketogenic Diet as a Therapy for Recurrent or Progressive and Refractory Brain Tumors in Children

Pilot Study of a Strict Classic Ketogenic Diet as a Therapy for Recurrent or Progressive and Refractory Brain Tumors in Children

This is a pilot study to test the feasibility of implementing a strict classic ketogenic diet among a population of children with recurrent or progressive and refractory brain tumors. Eligible participants will be admitted to the neurosciences floor for 5 days to begin the ketogenic diet either orally, by gastrostomy tube or via nasogastric tube. During the inpatient stay, they will be extensively educated on the diet restrictions and rules. Participants will then continue on the diet at home returning about 17 times over the next 12 months. Daily logs will be kept tracking diet changes, bowel movements and urine ketones. Blood will be collected during the inpatient stay and at all visits for both standard clinical care and research testing.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Brain Tumor, Childhood; Ketogenic Diet
• Intervention / Treatment: Other: Strict Classic Ketogenic Diet

Detailed Description

Primary Objective is to determine the feasibility (safety and tolerability) of a strict classic ketogenic diet among a population of children with recurrent or progressive and refractory brain tumors.

Secondary Objectives are: (1) to determine the objective response rate (complete response + partial response) to a strict classic ketogenic diet among children with recurrent or progressive and refractory brain tumor; (2) to estimate the time interval to tumor progression (Progression-Free Survival), time to treatment failure (Event-Free Survival), and time to death (Overall Survival) after initiation of a strict classic ketogenic diet among a group of pediatric patients with recurrent or progressive and refractory brain tumors; and (3) to describe and characterize tolerability and toxicities from a strict classic ketogenic diet among children with recurrent or progressive and refractory brain tumors.

Exploratory Objective: Identify biomarker correlates, including MR spectroscopy and metabolites of tumor response to a strict classic ketogenic diet.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel Bowers, MD; Phone Number: 214-456-2382; Email: Daniel.Bowers@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • The University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: Patients must be < 21 years of age inclusive at the time of enrollment on this protocol.
• Histologic Diagnosis: Histologically proven, primary brain tumor that is recurrent or progressive and refractory (nonresponsive) to standard, accepted therapy. A histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all subjects, except for diffuse intrinsic pontine glioma (DIPG).
• Measurable Disease: Patients must have radiographically documented measurable tumor as assessed by RANO or RAPNO criteria.
• Cranial and Spinal MRI: To document the degree of residual tumor, all patients must have an MRI of the brain with and without gadolinium performed within 2 weeks prior to study enrollment. For patients who undergo a tumor debulking surgery at the time of recurrence/progression, the following must be obtained:
• Cranial pre-operative MRI scan with and without contrast.
• Cranial post-operative MRI scan with and without contrast within 28 days following surgery. If possible, post-operative MRI should be performed within 48 hours of surgery, prior to the onset of edema or post-operative surgical enhancement, which can make measurements of residual tumor difficult.
• Performance Level: Patients must have a performance status of > 50. Use Karnofsky score for patients > 16 years of age and Lansky score for patients ≤ 16 years of age.
• Life Expectancy: Patients must have a life expectancy of > 8 weeks.
• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, biologic therapy, or radiotherapy prior to entering this study
• Growth factor(s): Must not have received within 1 week prior to entry onto this study.
• Other anti-cancer or experimental agents or therapies are not permitted. Homeopathic medicines are not permitted. Multivitamins are permitted.
• Organ Function Requirements: Adequate bone marrow, renal, liver, pulmonary, and central nervous system function
• All patients and/or their parents or legal guardians must sign a written informed consent.
• In the investigator's opinion, patients must have the ability to adhere to or tolerate the dietary protocol.
• Patients must be able to eat by mouth or must be willing to have a nasogastric tube (NGT) if gastrostomy tube is not already present.

Exclusion Criteria:

• Pregnancy
• Pregnant or breastfeeding. Female patients of childbearing potential must have negative pregnancy test result within the previous 14 days..
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation.
• Other Exclusionary Criteria: Disorder of B-oxidation, as measured by plasma aceyl-carnitine, Uncontrolled infection, History of nephrolithiasis, Diagnosis of diabetes mellitus that is being treated by medication.
• The following medications are excluded: Steroids: Therapeutic systemic doses of steroids must be stopped greater than 2 weeks prior to admission to the hospital to start the diet. A steroid washout of 1 week is acceptable for patients with DIPG. Concomitant chemotherapy drugs and homeopathic drugs are not permitted.

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

Other: Strict Classic Ketogenic Diet Arm; The classic ketogenic diet is individually calculated for each patient based on age, weight, and nutritional needs. The diet is typically administered from a 2:1 to 4:1 ratio; this means 2 to 4 parts of fat to 1 part of both protein (calculated based on RDA and whatever remaining portion of carbohydrates. The basis of calculations is first on the amount of required protein needed to meet RDA to insure adequate growth. Fine tuning of ketogenic diet therapy is based on serum beta-hydroxybutyrate levels (target levels of 3.5-6.5 mmol/L), tolerance of the diet, and response to treatment.

Other: Strict Classic Ketogenic Diet; Diet is administered from a 2:1 to 4:1 ratio; this means 2 to 4 parts of fat to 1 part of both protein (calculated based on RDA and whatever remaining portion of carbohydrates.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility (safety and tolerability) of the ketogenic diet	Defined by the enrolled subject completing 28 days of ketogenic diet therapy without grade 3 - 5 adverse events. These will be assessed via NCI's CTCAE v5.0 toxicity criteria.	28 days

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Daniel Bowers, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Central Nervous System Neoplasms; Nervous System Neoplasms; Recurrence; Brain Neoplasms
• Other Study ID Numbers: STU-2019-0853

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No