Asciminib With or Without Sildenafil for Brain Tumors

Study Purpose

Dissemination of medulloblastoma is an independent risk factor of poor prognosis. Dissemination of medulloblastoma at recurrence is nearly universally fatal. ABL1 and 2 have been recently found to mediate the dissemination of medulloblastoma. Genetically inactivating ABL1 and 2 resulted in decreased leptomeningeal medulloblastoma and improved overall survival (OS) in rodent models. Asciminib is an FDA approved for the treatment of chronic myeloid leukemia and is well tolerated, likely due to its specificity for ABL1 and ABL2. Asciminib is a P-glycoprotein (P-gp) substrate and thus may be susceptible to being pumped out of tumor cells and brain endothelial cells. It is unclear if asciminib can enter the central nervous system (CNS) and brain tumors in adequate concentration to have anti-tumor effects.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	6 Years - 25 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Ages 6-25 years old.

- Radiographic evidence of a recurrent/progressive brain tumor.

- Tumor must be predominantly in an intraparenchymal location.

- Deemed operable (able to be resected or have an open or stereotactic needle biopsy) by treating neurosurgeon.

- Karnofsky/Lansky Performance Status of ≥ 60.

Patients who are unable to walk because of paralysis but who are up in a wheelchair will be considered ambulatory for the purposes of the performance score.

- Bone Marrow: - ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported).

- Platelets ≥ 100,000/µl (may be supported by transfusion).

- Hemoglobin > 8 g/dL (may be supported by transfusion).

- Renal: - Serum creatinine ≤ upper limit of institutional normal.

- Hepatic: - Bilirubin ≤ 1.5 times upper limit of normal for age.

- ALT (SGPT) ≤ 3 times institutional upper limit of normal for age.

- AST (SGOT) ≤ 3 times institutional upper limit of normal for age.

- Ability to understand and willingness to sign an IRB approved written informed consent document.

Legally authorized representatives may sign and give informed consent on behalf of study participants. All patients and/or their parents or legal guardians must sign an IRB approved written informed consent document.

Exclusion Criteria:

- Tumors suspected to be pituitary tumors or tumors of the meninges.

- Unable to take tablets orally.

- Pregnant and/or breastfeeding.

Subjects of childbearing potential must have a negative serum or urine pregnancy test within 10 days prior to Day 1.

- Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness.

- Known immunosuppressive disease or human immunodeficiency virus infection.

- Any active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.

- Any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).

- Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07039760
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Washington University School of Medicine
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Eric Thompson, M.D.
Principal Investigator Affiliation	Washington University School of Medicine
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Tumor
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: Group A: Asciminib

Patients will receive a single dose of 120 mg oral asciminib 3 (+/- 1.5) hours prior to surgical resection or biopsy.

Experimental: Group B: Asciminib + Sildenafil

Patients will receive a single dose of 120 mg oral asciminib 3 (+/- 1.5) hours prior to surgical resection or biopsy and a single 20 mg oral dose of sildenafil 3 (+/- 1.5) hours prior to asciminib.

Interventions

Drug: - Asciminib

Commercially available stock

Drug: - Sildenafil

Commercially available stock

Procedure: - Surgical resection or biopsy

Standard of care

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Saint Louis, Missouri

Status

Address

Washington University School of Medicine/St. Louis Children's Hospital

Saint Louis, Missouri, 63110

Site Contact

Eric Thompson, M.D.

[email protected]

314-454-4707

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