What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as Sorafenib (a kinase inhibitor), Valproic Acid (an HDAC inhibitor), and Sildenafil (a PDE5 inhibitor), have various side effects. Sorafenib can cause hand-foot skin reactions, diarrhea, hypertension, and fatigue. Valproic Acid may lead to gastrointestinal disturbances, tremors, weight gain, and hepatotoxicity. Sildenafil is associated with headaches, flushing, dyspepsia, and visual disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

FDA-approved treatments for brain tumors include bevacizumab, a monoclonal antibody targeting VEGF, which is used for recurrent glioblastoma. Kinase inhibitors like sunitinib have been studied for recurrent meningiomas, showing some efficacy. HDAC inhibitors such as vorinostat have been explored in clinical trials for brain tumors, though not specifically approved for this indication. PDE5 inhibitors like sildenafil are not commonly used for brain tumors but are being investigated in combination therapies. These treatments reflect ongoing efforts to target various molecular pathways in brain tumor management.

What other types of research exist?

Promising novel alternatives for brain tumor treatment include: <ol> <li>Bevacizumab (anti-VEGF therapy) - shown efficacy in vestibular schwannomas and gliomas.</li> <li></li> </ol> Everolimus (mTORC1 inhibitor) - demonstrated effectiveness in meningiomas and vestibular schwannomas. 3. Ivosidenib (mutant-IDH1 inhibitor) - well tolerated with promising results in IDH1-mutant gliomas. 4. Vorasidenib (dual mutant-IDH1/2 inhibitor) - currently in phase III trials for IDH1/2-mutant gliomas. 5. PD-1 blockade (e.g., Nivolumab) - effective in recurrent atypical/anaplastic meningiomas.

← Back to Search

Phosphodiesterase Type 5 Inhibitor

Triple Drug Therapy for Brain Tumor

Phase 2

Waitlist Available

Led By Andrew Poklepovic, MD

Research Sponsored by Virginia Commonwealth University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Pathologically confirmed high-grade glioma (World Health Organization (WHO) grade 3 or 4), with documented computed tomography (CT) or magnetic resonance imaging (MRI) progression or recurrence. Biopsy is also an acceptable method of confirming progression or recurrence. If initial tumor was grade 2 glioma, histological confirmation of high-grade recurrence is required

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Must not have

Prior bevacizumab or tyrosine-kinase inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from initiation of study treatment to time of best response or off-study (up to 4 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three drugs to treat patients with recurring or worsening high-grade brain tumors. The treatment aims to stop tumor growth, make it easier to treat, and help the drugs reach the tumor more effectively. Bevacizumab is a monoclonal antibody that has shown significant clinical activity in recurrent malignant glioma.

Who is the study for?

This trial is for adults with high-grade glioma, a serious brain tumor that has come back after treatment. They must understand the study and agree to use birth control. Their blood counts and organ functions need to meet specific levels, they should be relatively active (able to care for themselves), and not have used certain drugs recently or have conditions that could interfere with the treatments.

What is being tested?

The trial tests if combining three drugs—sorafenib (Nexavar®), valproic acid (Depakote®), and sildenafil (Viagra®)—is safe and effective against recurrent high-grade glioma. It checks how well patients tolerate this mix of medications and observes their impact on the brain tumor's progression.

What are the potential side effects?

Possible side effects from these drugs include fatigue, skin reactions, digestive issues like nausea or diarrhea, increased risk of bleeding or bruising due to low platelet count, liver problems indicated by abnormal blood tests, changes in heart rhythm or rate, as well as potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My brain tumor has worsened or come back, confirmed by tests or biopsy.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have previously been treated with bevacizumab or a tyrosine-kinase inhibitor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from initiation of study treatment to time of best response or off-study (up to 4 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from initiation of study treatment to time of best response or off-study (up to 4 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from initiation of study treatment to time of best response or off-study (up to 4 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With 6-Month Progression Free Survival (PFS)

Secondary study objectives

Evaluation of Safety and Toxicity of Sorafenib, Valproic Acid, and Sildenafil

Number of Participants Whose Tumors Express PDGFRa With Best Response of CR Plus Number of Participants Whose Tumor Expresses PDGFRa With Best Response of PR.

Number of Participants Whose Tumors Express PDGFRa With and Without 12-Month OS.

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (sorafenib tosylate, valproic acid, sildenafil)Experimental Treatment3 Interventions

* Sorafenib 400 mg orally twice a day; * Valproic acid (to levels ≥ Lower Level of Normal (LLN) orally twice a day; * Sildenafil 50 mg orally twice a day A cycle consists of 4 weeks. \*The first 6 patients evaluable for qualifying toxicity assessment will be treated as a safety lead-in; enrollment will be gated (the first 3 evaluable patients must complete 4 weeks of the combination therapy before the next 3 patients start combination treatment on protocol)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

valproic acid

2003

Completed Phase 4

~330

sildenafil citrate

2011

Completed Phase 4

~710

sorafenib tosylate

2005

Completed Phase 2

~920

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Kinase inhibitors, such as Sorafenib, work by blocking specific enzymes (kinases) that promote tumor cell growth and survival, thereby inhibiting cancer progression. HDAC inhibitors, like Valproic Acid, function by altering gene expression through the inhibition of histone deacetylases, leading to the activation of tumor suppressor genes and induction of cancer cell death. PDE5 inhibitors, such as Sildenafil, increase intracellular levels of cyclic GMP, which can enhance the effectiveness of other anticancer agents and improve blood flow to the tumor, potentially increasing drug delivery. These mechanisms are crucial for brain tumor patients as they target different pathways involved in tumor growth and survival, offering a multifaceted approach to treatment and potentially improving outcomes.

Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas.Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies.