RECRUITING

Atovaquone Combined with Radiation in Children with Malignant Brain Tumors

Conditions

High-grade Glioma Medulloblastoma Diffuse Intrinsic Pontine Glioma Diffuse Midline Glioma, H3 K27M-Mutant Atovaquone Progression-free survival

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma/diffuse midline glioma/diffuse intrinsic pontine glioma (pHGG/DMG/DIPG). The secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of RT and before progression.

Official Title

Atovaquone Combined with Radiation in Children with Malignant Brain Tumors

Quick Facts

Study Start:2025-01

Study Completion:2027-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06624371

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years to 25 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Newly diagnosed pHGG/DMG/DIPG Patients must have histologically confirmed pediatric high-grade glioma (pHGG, WHO Grade 3 or 4) or diffuse midline glioma with altered H3K27 (DMG, WHO Grade 4). Primary pHGG or DMG spinal tumors are eligible. Diffuse intrinsic pontine glioma (DIPG) defined by MRI does not require histological confirmation. * Weight \> 10kg * Karnofsky and Lansky performance score \> 50% * Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible. * Adequate liver function defined as: * Total bilirubin ≤ 2x upper limit of normal (ULN) and * AST (SGOT) and ALT (SGPT) ≤ 225 U/L (5x the ULN). The ULN for AST and ALT will be 45 U/L. * Patients must have normal organ and marrow function as defined below: * absolute neutrophil count \> 1,000/mcL * platelets \> 100,000/mcL * hemoglobin \> 8g/dL * Total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \< 5 x (\<10 x if taking steroids) the institutional upper limit of normal * creatinine within normal institutional limits for age 2 OR * creatinine clearance \> 60mL/min/1.73 m for patients with creatinine levels above institutional normal * Relapsed, progressive pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of standard radiation therapy without prior atovaquone exposure and before progression. Patients with metastatic disease are allowed for Stratum 2 only. * Patients must have previously undergone standard-of-care treatment including surgery, radiation, and/or first-line adjuvant chemotherapy before the experimental treatment (atovaquone). * Patients must have recovered from the acute treatment-related toxicities (defined as \< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed. * Age \> 2 to 25 years * Weight \> 10kg * Karnofsky and Lansky performance score \> 50% * Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible. * Patients must have normal organ and marrow function as defined above for Stratum 1 * Adequate liver function is defined as: 1. Total bilirubin ≤ 2x upper limit of normal (ULN) and 2. AST (SGOT) and ALT (SGPT) ≤ 225 U/L (5x the ULN). The ULN for AST and ALT will be 45 U/L.	* Chronic systemic concurrent illness * Concurrent or history of anti-cancer therapy other than RT * Patients with metastatic tumor are excluded for Stratum 1 only. * Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded. * Patients must fully recover from all acute effects of prior surgical intervention. * History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone. * Symptomatic intratumoral hemorrhage, or asymptomatic intratumoral hemorrhage larger than punctate foci, at any time prior to enrollment. * Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion. * Concurrent illness * Patients must have recovered from all prior therapy as follows: 1. Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks before study enrollment or at least six (6) weeks if prior nitrosourea. 2. Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days before study enrollment. 3. Antibodies: ≥ 21 days must have elapsed from an infusion of the last dose of antibody and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed before enrollment. 4. Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days before enrollment. 5. Radiation: Patients must have had their last fraction of • Craniospinal irradiation ≥ 3 months before enrollment. • Other substantial bone marrow irradiation ≥ 6 weeks before enrollment • Local or palliative XRT (small port) ≥ 2 weeks. 6. Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow/stem cell transplant before enrollment. Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded. * Patients must fully recover from all acute effects of prior surgical intervention. * History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone. * Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.

Inclusion Criteria

Exclusion Criteria

* Newly diagnosed pHGG/DMG/DIPG Patients must have histologically confirmed pediatric high-grade glioma (pHGG, WHO Grade 3 or 4) or diffuse midline glioma with altered H3K27 (DMG, WHO Grade 4). Primary pHGG or DMG spinal tumors are eligible. Diffuse intrinsic pontine glioma (DIPG) defined by MRI does not require histological confirmation.
* Weight \> 10kg
* Karnofsky and Lansky performance score \> 50%
* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.
* Adequate liver function defined as:
* Total bilirubin ≤ 2x upper limit of normal (ULN) and
* AST (SGOT) and ALT (SGPT) ≤ 225 U/L (5x the ULN). The ULN for AST and ALT will be 45 U/L.
* Patients must have normal organ and marrow function as defined below:
* absolute neutrophil count \> 1,000/mcL
* platelets \> 100,000/mcL
* hemoglobin \> 8g/dL
* Total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) \< 5 x (\<10 x if taking steroids) the institutional upper limit of normal
* creatinine within normal institutional limits for age 2 OR
* creatinine clearance \> 60mL/min/1.73 m for patients with creatinine levels above institutional normal
* Relapsed, progressive pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of standard radiation therapy without prior atovaquone exposure and before progression. Patients with metastatic disease are allowed for Stratum 2 only.
* Patients must have previously undergone standard-of-care treatment including surgery, radiation, and/or first-line adjuvant chemotherapy before the experimental treatment (atovaquone).
* Patients must have recovered from the acute treatment-related toxicities (defined as \< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed.
* Age \> 2 to 25 years
* Weight \> 10kg
* Karnofsky and Lansky performance score \> 50%
* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.
* Patients must have normal organ and marrow function as defined above for Stratum 1
* Adequate liver function is defined as:
1. Total bilirubin ≤ 2x upper limit of normal (ULN) and
2. AST (SGOT) and ALT (SGPT) ≤ 225 U/L (5x the ULN). The ULN for AST and ALT will be 45 U/L.

* Chronic systemic concurrent illness
* Concurrent or history of anti-cancer therapy other than RT
* Patients with metastatic tumor are excluded for Stratum 1 only.
* Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.
* Patients must fully recover from all acute effects of prior surgical intervention.
* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.
* Symptomatic intratumoral hemorrhage, or asymptomatic intratumoral hemorrhage larger than punctate foci, at any time prior to enrollment.
* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.
* Concurrent illness
* Patients must have recovered from all prior therapy as follows:
1. Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks before study enrollment or at least six (6) weeks if prior nitrosourea.
2. Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days before study enrollment.
3. Antibodies: ≥ 21 days must have elapsed from an infusion of the last dose of antibody and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed before enrollment.
4. Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days before enrollment.
5. Radiation: Patients must have had their last fraction of • Craniospinal irradiation ≥ 3 months before enrollment. • Other substantial bone marrow irradiation ≥ 6 weeks before enrollment • Local or palliative XRT (small port) ≥ 2 weeks.
6. Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow/stem cell transplant before enrollment. Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.
* Patients must fully recover from all acute effects of prior surgical intervention.
* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.
* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.

Contacts and Locations

Study Contact

Tobey MacDonald, MD

CONTACT

404-727-1447

aflacdevtreferral@choa.org

Amber Kaminski

CONTACT

aflacdevtreferral@choa.org

Principal Investigator

Tobey MacDonald, MD

PRINCIPAL_INVESTIGATOR

Emory University

Study Locations (Sites)

Arthur M Blank Hospital

Atlanta, Georgia, 30329

United States

Children's Healthcare of Atlanta: Scottish Rite

Atlanta, Georgia, 30342

United States

Collaborators and Investigators

Sponsor: Emory University

Tobey MacDonald, MD, PRINCIPAL_INVESTIGATOR, Emory University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01

Study Completion Date2027-10

Study Record Updates

Study Start Date2025-01

Study Completion Date2027-10

Terms related to this study

Keywords Provided by Researchers

Atovaquone
Progression-free survival

Additional Relevant MeSH Terms

High-grade Glioma
Medulloblastoma
Diffuse Intrinsic Pontine Glioma
Diffuse Midline Glioma, H3 K27M-Mutant