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Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

Primary Purpose

Pediatric Brain Tumor

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ketogenic diet
BCNU
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pediatric Brain Tumor

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept 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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketogenic Diet

Arm 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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 20, 2018
Last Updated
December 7, 2022
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03591861
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
November 1, 2022 (Actual)
Study Completion Date
November 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Brain Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketogenic Diet
Arm Type
Experimental
Arm 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
Intervention Type
Procedure
Intervention Name(s)
Ketogenic diet
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BCNU
Other Intervention Name(s)
Carmustine, BiCNU
Intervention Description
-Standard of care
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
Through completion of enrollment of all participants (estimated to be 3 years)
Title
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
Description
-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
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 2 years
Title
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)
Description
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.
Time Frame
Up to 10 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Cluster, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Therapeutic Targeting of Sex Differences in Pediatric Brain Tumor Glycolysis

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