Asciminib With or Without Sildenafil for Brain Tumors

NCT07039760 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 202509139
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Tumor

Keywords

Asciminib; Sildenafil; ABL1; ABL2; Tyrosine kinase inhibitor; Pediatric brain tumor; Brain tumor; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• Tumor:plasma ratio of asciminib

  At time of surgical resection or biopsy (day 1)

• Tumor:plasma ratio of asciminib with sildenafil

  At time of surgical resection or biopsy (day 1)

Secondary Outcomes (4)

• Change in plasma levels of asciminib

  Baseline, time of tumor resection/biopsy (day 1), and 8 (+/- 4 hours) after surgical resection or biopsy

• Expression of c-MYC in brain tumor specimens

  At time of surgical resection or biopsy (day 1)

• Expression of p-CRKL in brain tumor specimens

  At time of surgical resection or biopsy (day 1)

• Proportion of patients with unacceptable toxicity

  From start of treatment (day 1) through 3 weeks following asciminib

Study Arms (2)

Group A: Asciminib

EXPERIMENTAL

Patients will receive 1.3 mg/kg oral asciminib 12 +/- 1.5 hours prior to a second dose of 1.3 mg/kg oral asciminib. Surgery or biopsy will take place 3 +/- 1.5 hours after last dose.

Drug: Asciminib; Procedure: Surgical resection or biopsy

Group B: Asciminib + Sildenafil

EXPERIMENTAL

Patients will receive 1.3 mg/kg oral asciminib plus 20 mg sildenafil (10 mg if \< 20 kg) 12 +/- 1.5 hours prior to a second dose of 1/3 mg/kg asciminib plus 20 mg (10 mg if \< 20 kg) sildenafil. Surgery or biopsy will take place 3 +/- 1.5 hours after last dose.

Drug: Asciminib; Drug: Sildenafil; Procedure: Surgical resection or biopsy

Interventions

Asciminib DRUG

Commercially available stock

Group A: Asciminib; Group B: Asciminib + Sildenafil

Sildenafil DRUG

Commercially available stock

Group B: Asciminib + Sildenafil

Surgical resection or biopsy PROCEDURE

Standard of care

Group A: Asciminib; Group B: Asciminib + Sildenafil

Eligibility Criteria

• Age: 6 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 6-25 years old, inclusive.
• 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.

You may not qualify if:

• Tumors suspected to be pituitary tumors or tumors of the meninges.
• Diagnosis of atypical teratoid rhabdoid tumor (ATRT) or diagnosis of pilocytic astrocytoma (PA).
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

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

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Brain Neoplasms

Interventions

asciminib; Sildenafil Citrate; Biopsy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Eric Thompson, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Thompson, M.D.

CONTACT

314-454-4707; pedshemonctrialreferral@wustl.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: June 26, 2025
• Study Start: April 30, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)