Clinical trial NCT03591861: Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis
Official title: Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Pediatric Brain Tumor
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2018-07-19
Enrollment: 2
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Through completion of enrollment of all participants (estimated to be 3 years)
measure: 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
timeFrame: Up to 2 years
Secondary outcomes:
measure: 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
timeFrame: Up to 2 years
measure: 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)
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Andrew Cluster, M.D.
role: PRINCIPAL_INVESTIGATOR
References: