Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

The Washington University

Status: Terminated

Conditions: Pediatric Brain Tumor

Treatments: Drug: BCNU; Procedure: Ketogenic diet

Study type: Interventional

Funder types: Other

Identifiers

NCT03591861

201806141

Details and patient eligibility

About

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.

Enrollment: 2 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Ketogenic Diet

Experimental group

Description:

* 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

Treatment:

Drug: BCNU

Procedure: Ketogenic diet