Asciminib + Sildenafil for Brain Cancer

Overseen By Eric Thompson, M.D.

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Disqualifiers: Pituitary tumors, Meningeal tumors, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a combination of two drugs, asciminib and sildenafil, can treat recurrent brain tumors. Researchers aim to determine if asciminib, a targeted therapy, can effectively reach and impact brain tumors due to its specific targeting of proteins linked to tumor spread. Participants will receive either asciminib alone or in combination with sildenafil before surgery or a biopsy. Those with a recurrent or growing brain tumor that can be surgically treated might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that asciminib is generally safe for people. It has been used to treat chronic myeloid leukemia, and studies have found it to be safe over time, with no new safety issues. This suggests it might also be safe for other uses, such as treating brain cancer, but this is still under investigation.

Sildenafil, commonly known for treating erectile dysfunction, has also been found safe when used with other cancer treatments in early studies. The combination of asciminib and sildenafil remains in the early testing stages, so specific safety information for this mix in brain cancer is not yet available. However, both drugs have a history of being well-tolerated individually. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because asciminib offers a novel approach by targeting a specific protein involved in cancer cell growth, while sildenafil is typically used for other conditions but may enhance the effectiveness of asciminib. Asciminib works differently from traditional brain cancer treatments, which often involve surgery, radiation, or chemotherapy, by specifically inhibiting the BCR-ABL1 tyrosine kinase, a protein that contributes to cancer progression. The combination of asciminib with sildenafil is particularly intriguing because sildenafil might improve drug delivery to the brain, potentially making asciminib more effective. This innovative strategy is what sets these treatments apart from existing options, potentially leading to better outcomes for patients with brain cancer.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that asciminib effectively treats chronic myeloid leukemia (CML) by specifically blocking two proteins, ABL1 and ABL2, which aid in cancer spread. This is promising for brain cancer like medulloblastoma, as these proteins also contribute to its spread. In rodent studies, turning off these proteins reduced cancer spread and improved survival. In this trial, some participants will receive asciminib alone, while others will receive a combination of asciminib and sildenafil. Adding sildenafil to asciminib may enhance its ability to reach the brain, increasing its potential impact on brain tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Eric Thompson, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with brain cancer or tumors, specifically medulloblastoma that has spread. Participants must have undergone surgical resection or biopsy of the tumor. The study excludes those who might not safely receive the drugs due to other medical conditions, but specific exclusion criteria are not listed.

Inclusion Criteria

Bone Marrow: ANC ≥ 1000/µl, Platelets ≥ 100,000/µl, Hemoglobin > 8 g/dL

My brain tumor is growing again and is mainly inside the brain tissue.

My kidney function, measured by creatinine, is within normal range.

Exclusion Criteria

I do not have an active infection or fever without a known cause.

Pregnant and/or breastfeeding (negative pregnancy test required)

I have an immunosuppressive condition or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 120 mg oral asciminib, with or without a single 20 mg oral dose of sildenafil, prior to surgical resection or biopsy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib
• Sildenafil

Trial Overview The trial is testing Asciminib, approved for leukemia and known for its specificity in targeting certain proteins involved in tumor spread. It's being studied alone or combined with Sildenafil to see if it can effectively enter the brain and treat tumors there.

How Is the Trial Designed?

Group I: Group B: Asciminib + Sildenafil Experimental Treatment 3 Interventions

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 II: Group A: Asciminib Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Citations

1. ecancer.org ecancer.org/en/news/25799-ash-2024-longer-term-data-for-asciminib-reinforce-superior-efficacy-with-favourable-safety-and-tolerability-profile-in-adults-with-newly-diagnosed-cml

ASH 2024: Longer-term data for asciminib reinforce ... The asciminib MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%)1. Patients treated with asciminib ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11573869/

Clinical Pharmacology of Asciminib: A Review - PMC Asciminib has a unique mechanism of action (working by STAMP) and has shown very good efficacy in patients with chronic-phase CML even in the ...

3. onclive.com onclive.com/view/meta-analysis-highlights-efficacy-safety-benefits-with-asciminib-in-chronic-myeloid-leukemia

Meta-Analysis Highlights Efficacy, Safety Benefits With ... Findings showed that patients treated with asciminib achieved improved rates of major molecular response (MMR) compared with those administered ...

4. cancernetwork.com cancernetwork.com/view/superiority-of-asciminib-in-cml-cp-is-a-win-win-for-patients

Superiority of Asciminib in CML-CP Is a 'Win-Win' for Patients The 24-week MMR rate was 25.5% in the asciminib arm and 13.2% in the bosutinib arm, equating to a 12.2% difference between groups after ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06236724

Phase II Study Assessing Efficacy and Safety of Asciminib ... Phase II Study Assessing Efficacy and Safety of Asciminib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase.

6. haematologica.org haematologica.org/article/view/12134

Asciminib for Philadelphia chromosome-positive leukemias In ASCEMBL, patients on asciminib had a general trend to decreased severity of CML and treatment-related symptoms, and improved quality of life, ...

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety ...