Asciminib With or Without Sildenafil for Brain Tumors

Phase 1

Not yet recruiting

• Conditions: Brain Tumor
• Interventions: Drug: Asciminib; Procedure: Surgical resection or biopsy; Drug: Sildenafil

• Registration Number: NCT07039760
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-17
• Last Update Submitted: 2025-06-17
• Study First Posted: 2025-06-26
• Last Update Posted: 2025-06-26
• Study Start: 2025-12-01
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: Asciminib	Asciminib	Patients will receive a single dose of 120 mg oral asciminib 3 (+/- 1.5) hours prior to surgical resection or biopsy.
Group A: Asciminib	Surgical resection or biopsy	Patients will receive a single dose of 120 mg oral asciminib 3 (+/- 1.5) hours prior to surgical resection or biopsy.
Group B: Asciminib + Sildenafil	Asciminib	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.
Group B: Asciminib + Sildenafil	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.
Group B: Asciminib + Sildenafil	Surgical resection or biopsy	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Expression of c-MYC in brain tumor specimens	At time of surgical resection or biopsy (day 1)
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 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 2 weeks following asciminib

Trial Locations

Locations (1)

Washington University School of Medicine/St. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States