Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

Washington University School of Medicine2 enrolled

Overview

The investigators will develop the concept of a sex-specific therapeutic intervention for gliomas that is based upon dietary carbohydrate restriction. The investigators will integrate metabolomics tools and FDG-PET imaging to validate the ketogenic diet on a sex-specific basis.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pediatric Brain Tumor

Interventions

Ketogenic dietPROCEDURE

* Children under 2 years will immediately start on a full calorie classical 3:1 ketogenic diet. The 3:1 ratio indicates that the diet contains 3 g of fat for every 1 g of protein + carbohydrate, which results in about 87% of calories coming from fat. * Children 2 years or older will skip breakfast and lunch on the day of admission but start a full calorie 3:1 ketogenic diet at dinner.

BCNUDRUG

-Standard of care

Eligibility

Sex: ALLMax age: 21 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of a recurrent primary brain tumor with no curative therapy available. * Measurable disease using pediatric Response Assessment in Neuro-Oncology Criteria (RANO) criteria. * Life expectancy \> 12 weeks * Prior treatment with radiation alone, chemotherapy alone or combined radiation and chemotherapy is allowed. * Patient is \< 21 years of age * Normal bone marrow and organ function as defined below: * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcl * Platelets ≥ 100,000/mcl * Total bilirubin ≤ 1.5 x IULN * AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN * Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Normal room air oxygenation must be documented. If room air oxygen saturation is less than 97%, a diffusion capacity of carbon monoxide (DLCO) of greater than 80%, must be demonstrated. * Karnofsky or Lansky performance score of ≥ 60 * Patients of childbearing potential 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 female patient become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Patient does not have any of the following conditions as they are contraindicated for ketogenic diet: * Primary and secondary carnitine deficiency * Carnitine palmitoyltransferase I or II deficiency * Carnitine translocase deficiency * Mitochondrial β-oxidation defects * Pyruvate carboxylase deficiency * Glycogen storage diseases * Ketolysis defects * Ketogenesis defects * Porphyria * Prolonged QT syndrome * Liver insufficiency * Renal insufficiency * Pancreatic insufficiency * Pulmonary insufficiency * Hyper insulinism * Pregnant and/or breastfeeding. Female patients of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Feasibility of combining a ketogenic diet with chemotherapy in children with relapsed brain tumors as measured by the number of patients who can recruited with 3 years

* The study will be defined as being feasible if all 15 patients can be recruited within 3 years * Please note that feasibility of the study is dependent on both primary outcome measures

Time frame: Through completion of enrollment of all participants (estimated to be 3 years)

Feasibility of combining a ketogenic diet with chemotherapy in children with relapsed brain tumors as measured by if at least 80% of the patients comply with the intervention

-The study will be defined as being feasible if at least 80% of the patients comply with the intervention as defined as achieving 80% of the targeted level of ketosis as assessed from laboratory measures and 80% of the planned BCNU doses --Please note that feasibility of the study is dependent on both primary outcome measures

Time frame: Up to 2 years

Secondary Outcomes

Tolerability of combining a ketogenic diet with chemotherapy in male children with relapsed brain tumors versus female children with relapsed brain tumors as measured by toxicity

* All toxicities will be summarized by noting the count of participants who experience each toxicity * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

Time frame: Up to 2 years

Tumor response of male children with relapsed brain tumors to a ketogenic diet combined with chemotherapy versus female children with relapsed brain tumors as measured by progression-free survival (PFS)

* PFS is defined as the duration of time from start of treatment to time of radiographic progression or death due to any cause, whichever occurs first. * Progression will be defined by the Response Assessment in Neuro-Oncology (RANO) working group guideline.

Time frame: Up to 10 years

Data from ClinicalTrials.gov

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