This early phase I trial compares the effect of asciminib alone to asciminib in combination with sildenafil in treating patients with brain tumors that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). The blood-brain barrier is a kind of filter system in your brain that keeps out germs and other harmful substances that could cause damage. However, it also sometimes keeps out drugs and other chemicals that could potentially be used as treatments. Asciminib hydrochloride blocks the BCR::ABL1 fusion protein, which may help keep tumor cells from growing and may kill them. Asciminib hydrochloride is a type of tyrosine kinase inhibitor. Sildenafil, a type of phosphodiesterase inhibitor, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Sildenafil relaxes the smooth muscle cells resulting in relaxation and may help asciminib work better. Giving asciminib alone or in combination with sildenafil may be safe, tolerable and may cross the blood-brain barrier resulting in a potential treatment for patients with recurrent or progressive brain tumors.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07039760.
Locations matching your search criteria
United States
Missouri
Saint Louis
Siteman Cancer Center at Washington UniversityStatus: Approved
Contact: Eric M Thompson
Phone: 314-454-4707
Saint Louis Children's HospitalStatus: Approved
Contact: Eric M Thompson
Phone: 314-454-4707
PRIMARY OBJECTIVES:
I. To determine if orally-delivered asciminib can enter brain tumors in clinically relevant concentrations.
II. To determine if inhibiting P-glycoprotein (P-gp) increases the ability of asciminib to enter brain tumors.
SECONDARY OBJECTIVES:
I. To evaluate the pharmacokinetics (PK) of oral asciminib ± sildenafil citrate (sildenafil) in patients with brain tumors.
II. To establish if orally-delivered asciminib ± P-gp inhibition decreases the expression of ABL1/2 substrates in brain tumors (pharmacodynamics [PD]).
III. To evaluate for any adverse events related to oral asciminib hydrochloride (asciminib) and sildenafil.
EXPLORATORY OBJECTIVES:
I. To determine if orally-delivered asciminib can enter the cerebrospinal fluid (CSF) in clinically relevant concentrations.
II. To determine if inhibiting P-gp increases the ability of asciminib to enter the CSF.
III. To determine if orally-delivered asciminib can enter normal brain in clinical relevant concentrations.
IV. To determine if inhibiting P-gp increases the ability of asciminib to enter normal brain.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP A: Patients receive asciminib orally (PO) twice daily (BID) for two separate doses 12 hours apart on day 1 and then 3 hours after second dose, undergo surgical resection or tumor tissue biopsy. Additionally, patients undergo blood sample collection throughout the study.
GROUP B: Patients receive asciminib PO BID and sildenafil PO BID for two separate doses 12 hours apart on day 1 and then 3 hours after second dose, undergo surgical resection or tumor tissue biopsy. Additionally, patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed for at least 21 days.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorEric M Thompson
