Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

Pediatric Brain Tumor Clinical Trial

Official title:

Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03591861
• Other study ID #: 201806141
• Status: Terminated
• Phase: N/A
• Start date: May 1, 2019
• Est. completion date: November 1, 2022

Study information

• Verified date: December 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: November 1, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Brain Neoplasms
• Pediatric Brain Tumor

Intervention

Procedure:
• Ketogenic diet
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.

Drug:
• BCNU
-Standard of care

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Through completion of enrollment of all participants (estimated to be 3 years)
Primary	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	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 10 years

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine