Verteporfin (Visudyne) for Glioblastoma

Overseen By William L. Read, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Emory University

Disqualifiers: Pregnancy, Hereditary porphyria, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks per cycle

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of Visudyne (liposomal verteporfin) and to see how well it works in treating patients with high grade EGFR-mutated glioblastoma that has come back (recurrent). Visudyne is FDA approved in combination with light to treat eye diseases. In this study we use Visudyne by itself like chemotherapy to kill tumor cells which may be sensitive to verteporfin.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must stop any prior chemotherapy treatments for glioma at least 7 days before starting the study. If you are on bevacizumab, you may continue it while participating in the trial.

What makes the drug Verteporfin unique for treating glioblastoma?

Verteporfin is unique for treating glioblastoma because it is primarily used as a photosensitizer in photodynamic therapy for eye conditions, and its application in brain tumors like glioblastoma is novel, potentially offering a different mechanism of action compared to traditional chemotherapy or radiation. ^{1 2 3 4 5}

Research Team

William L Read, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with recurrent grade 4 glioblastoma that has EGFR mutations, who've had standard treatments including radiation and temozolomide. They may be on bevacizumab but not exclusively for anti-edema effects. Participants must have MRI evidence of tumor progression, agree to central venous access placement, and use effective contraception. ECOG performance status should be between 0-3.

Inclusion Criteria

I have stopped any cancer treatments, including chemotherapy, at least 7 days ago.

All participants must sign a written informed consent

I am currently using an Optune device and want to keep using it.

Exclusion Criteria

I have swelling that improved with bevacizumab, but my tumor still grew.

Persons who are deemed to have progression on clinical grounds only (new symptoms, declining PS) are ineligible. In the absence of MRI change one cannot be confident that clinical deterioration is a direct result of tumor progression, and could be due to intercurrent illness

I don't have severe health issues, except for brain tumor-related problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive verteporfin intravenously over 83 minutes weekly for 6 weeks in cycle 1, then weekly for 5 weeks in subsequent cycles. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

6 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 12 weeks.

30 days initial follow-up, then every 12 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival up to 2 years.

Up to 2 years

Treatment Details

Interventions

• Verteporfin

Trial Overview The study tests the safety and optimal dosage of Visudyne (liposomal verteporfin), typically used for eye diseases, as a solo treatment like chemotherapy targeting sensitive tumor cells in high-grade EGFR-mutated glioblastoma patients.

Participant Groups

Group I: Treatment (verteporfin) Experimental Treatment 1 Intervention

Patients receive verteporfin IV over 83 minutes weekly for 6 weeks in cycle 1, then weekly for 5 weeks in subsequent cycles. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Verteporfin is already approved in United States, European Union for the following indications:

Approved in United States as Visudyne for:

• Predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration
• Predominantly classic subfoveal choroidal neovascularization due to pathologic myopia
• Predominantly classic subfoveal choroidal neovascularization due to presumed ocular histoplasmosis

Approved in European Union as Visudyne for:

• Predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration
• Predominantly classic subfoveal choroidal neovascularization due to pathologic myopia
• Predominantly classic subfoveal choroidal neovascularization due to presumed ocular histoplasmosis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of bevacizumab (BEV) and vorinostat (VOR) was well tolerated in patients with recurrent glioblastoma, with a 6-month progression-free survival (PFS6) rate of 30% and a median overall survival (OS) of 10.4 months based on a study of 40 patients.

Despite being well tolerated, the combination therapy did not show an improvement in PFS6 or median OS compared to BEV alone, indicating that adding VOR may not enhance the effectiveness of BEV in treating recurrent glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma. Ghiaseddin, A., Reardon, D., Massey, W., et al.[2019]

Vinblastine (VBL) was used to treat a 7-month-old girl with progressive low-grade glioma, resulting in a significant increase in liver enzymes (grade IV toxicity) that resolved after treatment ended.

The case suggests that younger patients may experience different toxicity profiles with VBL, indicating a need for age-specific toxicity screening in future treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient Hepatotoxicity Induced by Vinblastine in a Young Girl with Chiasmatic Low Grade Glioma. Franke, NE., Blok, GJ., Voll, ML., et al.[2021]

Spirohydantoin mustard (spiromustine) is a promising therapy for glioblastoma multiforme that effectively penetrates the blood-brain barrier and targets brain tumors, potentially improving treatment outcomes.

Intracarotid administration of cisplatin enhances drug delivery directly to the tumor while minimizing systemic exposure, indicating a strategic approach to chemotherapy for better efficacy and safety in treating this aggressive brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. Resio, MJ., DeVroom, HL.[2019]

The VM spontaneous murine astrocytoma model effectively mimics human malignant glioma, allowing for reliable testing of cytotoxic drugs.

Drugs like BCNU, CCNU, and vincristine significantly reduced tumor volume and increased survival in treated mice, while procarbazine showed no effectiveness, highlighting the potential of these agents in glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemotherapeutic response of a murine (VM) model of human glioma. Bradford, R., Darling, JL., Thomas, DG.[2019]

In a phase I study involving 15 patients with glioblastoma multiforme (GBM), the combination of vistusertib and temozolomide (TMZ) was well tolerated, with most side effects being mild (grade 1-2) such as fatigue and gastrointestinal symptoms.

The treatment showed preliminary efficacy, with 8% of patients achieving a partial response and 38% having stable disease, indicating that this combination may provide a beneficial option for patients experiencing recurrence of GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study. Lapointe, S., Mason, W., MacNeil, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma. [2019]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Transient Hepatotoxicity Induced by Vinblastine in a Young Girl with Chiasmatic Low Grade Glioma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The chemotherapeutic response of a murine (VM) model of human glioma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study. [2021]