Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

NCT03591861 | Terminated DMC

• 1 other identifier: 201806141
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pediatric Brain Tumor

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (2)

• 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

  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)

  Up to 10 years

Study Arms (1)

Ketogenic Diet

EXPERIMENTAL

* Caregivers (and participating children) attend intro ketogenic diet class (4 - 30 min lectures) * Clinic visit with neurologist, nurse, and dietitian prior to hospital admission and then once every 3 months * Laboratory studies prior to hospital admission and then at each follow-up visit * Hospital admission (3-5 day) to start the ketogenic diet * Standard of care chemotherapy with BCNU for up to 2 years * Ketogenic diet can continue for up to 2 years

Procedure: Ketogenic diet; Drug: BCNU

Interventions

Ketogenic diet PROCEDURE

* 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.

Ketogenic Diet

BCNU DRUG

-Standard of care

Also known as: Carmustine, BiCNU

Ketogenic Diet

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Interventions

Diet, Ketogenic; Carmustine

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Andrew Cluster, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 19, 2018
• Study Start: May 1, 2019
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 12, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)