Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

• ClinicalTrials.gov Identifier: NCT03591861
• Recruitment Status: Recruiting
• First Posted: July 19, 2018
• Last Update Posted: May 4, 2021
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Brain Tumor	Procedure: Ketogenic diet; Drug: BCNU	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis
• Actual Study Start Date: May 1, 2019
• Estimated Primary Completion Date: May 31, 2024
• Estimated Study Completion Date: May 31, 2032

Arms and Interventions

Arm

Intervention/treatment

Experimental: Ketogenic Diet; 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; 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; Other Names: Carmustine; BiCNU

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Up to 2 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
2. 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 [ Time Frame: Up to 2 years ]

   -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

Secondary Outcome Measures :

1. 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 [ Time Frame: Up to 2 years ]
   • 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.
2. 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) [ Time Frame: Up to 10 years ]
   • 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.

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Andrew Cluster, M.D.; 314-273-1451; acluster@wustl.edu

Locations

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Andrew Cluster, M.D. 314-273-1451 acluster@wustl.edu

Principal Investigator: Andrew Cluster, M.D.

Sub-Investigator: Joseph Ippolito, M.D., Ph.D.

Sub-Investigator: Lin Lin Thio, M.D., Ph.D.

Sub-Investigator: Jingqin (Rosy) Luo, Ph.D.

Sub-Investigator: Joshua Rubin, M.D., Ph.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Andrew Cluster, M.D.; Washington University School of Medicine

More Information

Additional Information:

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

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03591861
• Other Study ID Numbers: 201806141
• First Posted: July 19, 2018
• Last Update Posted: May 4, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carmustine; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents