A Phase 1 / 2 Study of Visudyne (Liposomal Verteporfin) in Persons with Recurrent High Grade EGFR-Mutated Glioblastoma
Summary
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.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of successively higher doses of verteporfin (Visudyne \[liposomal verteporfin\]) and determine the maximum tolerated dose (MTD) in study participants with recurrent EGFR positive (+) glioblastoma (GBM). (Phase I) II. To evaluate the anti-tumor activity of Visudyne by assessing progression-free survival (PFS) and overall survival (OS). (Phase II) III. To describe the response rate of EGFR+ GBM in study participants treated with Visudyne. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the anti-tumor activity of Visudyne by assessing progression-free survival (PFS) and overall survival (OS). (Phase I) II. To describe the response rate of EGFR+ GBM in study participants treated with Visudyne. (Phase I) III. To describe pharmacokinetics of Visudyne administered on a weekly schedule. (Phase I) IV. To evaluate the safety and tolerability of successively higher doses of Visudyne in study participants with recurrent EGFR+ GBM. (Phase II) OUTLINE: This is a dose-escalation study. Patients receive verteporfin intravenously (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. After completion of study treatment, patients are followed up for 30 days and then every 12 weeks.
Arms & interventions
- DrugVerteporfin
Given IV
Outcome measures
Primary
Incidence of adverse events (Phase I)
Will be graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For each adverse event, information to be collected includes event description, time of onset, clinician assessment of severity, relationship to study product (assessed only by those with the training and authority to make a diagnosis), and time of resolution/stabilization of the event.
Time frame: From study enrollment until 100 days after the last day of study participation
Progression free survival (PFS) (Phase II)
Will be assessed by Response Assessment in Neuro-Oncology Criteria (RANO) for magnetic resonance imaging (MRI) of glioblastoma. Progression-free survival is defined as no progression within 6 weeks. Progression-free survival will be estimated as a binary rate, and a 95% confidence interval will be estimated using the Clopper-Pearson method.
Time frame: At 6 weeks
Response rate (RR) (Phase II)
Will be assessed by RANO for MRI of glioblastoma.
Time frame: From study enrollment until 2 years
Overall survival (Phase II)
Will be estimated using the Kaplan-Meier method.
Time frame: Time from study enrollment to death or last follow-up, assessed up to 2 years
Secondary
PFS (Phase I)
Time frame: From study enrollment to 2 years
RR (Phase I)
Time frame: From study enrollment to 2 years
Overall survival (Phase I)
Time frame: Time from study enrollment to death or last follow-up, assessed up to 2 years
Visudyne blood levels (Phase I)
Time frame: At timepoints following administration
Incidence of adverse events (Phase II)
Time frame: From study enrollment to 2 years
Eligibility criteria
Study locations (1)
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322