Verteporfin for the Treatment of Recurrent High Grade EGFR-Mutated Glioblastoma

Inclusion Criteria:

• Persons with recurrent or progressive grade 4 glioma (glioblastoma) are eligible forthis study. Participants should have received standard first line therapy includingradiation and temozolomide

• Eligible participants have tumors that show mutant or amplified EGFR. Thisdetermination can be made using standard of care mutation analysis panels (e.g.Snapshot). It is often assessed at diagnosis as part of standard of care

• Eligible participants must have evidence on magnetic resonance imaging (MRI) ofprogression. This may be as new or increased enhancement, or growth / increase innonenhancing abnormality. Care should be taken to distinguish those with trueprogression from those with radiation related changes. Persons with changes inenhancement possibly due in part or in whole to late radiation effect should receivebevacizumab as standard of care, and defer study participation

• Participants may be receiving bevacizumab, and show progression while onbevacizumab. These participants may continue bevacizumab while on study. Persons noton bevacizumab but who would benefit from the anti-edema effect of bevacizumabshould not enroll on this study but should proceed with bevacizumab alone, and deferenrollment until such time as they progress

• Visudyne is a vesicant. Participants will likely have poor veins, and will requirerepeated intravenous treatments. Participants must be willing to have placed acentral venous access, such as a portacath

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3. Participantswho are ECOG 2 or 3 should ideally have been in that situation for some time, andnot be in the midst of rapid clinical decline

• Medical comorbidities (excepting neurological) must be grade 2 or less if graded astoxicity

• Eligible participants may have grade 3 neurologic comorbidities (for exampleaphasia, ataxia) arising as a consequence of brain pathology

• Participants should be reasonably expected to be able to complete 6 weeks (1 cycle)of treatment on study before death or worsening of PS to 4 or 5

• Other anti-cancer medical treatments. Treatments in this category includechemotherapy and non-bevacizumab therapies. 7 days must have elapsed sincediscontinuation of prior chemotherapeutic treatments for glioma and study treatment.Participants may have had any number of prior treatments

• All participants on this study must have had prior radiation to the brain. Radiationmust have been completed 90 days prior to first study treatment

• 21 days must have elapsed since prior major surgery

• Participants already using a Novo-tumor treating fields therapy (TTF) (Optune)device and who wish to continue may do so

• All participants must sign a written informed consent

• The effects of study drugs used in this study on the developing human fetus areunknown. For this reason, female of child-bearing potential (FCBP) must have anegative serum or urine pregnancy test prior to starting therapy

• FCBP and men must agree to use adequate contraception (hormonal or barrier method ofbirth control; abstinence) prior to study entry and for the duration of studyparticipation and 8 weeks after. Should a woman become pregnant or suspect she ispregnant while she or her partner is participating in this study, she should informher treating physician immediately. Men treated or enrolled on this protocol mustalso agree to use adequate contraception prior to the study, for the duration ofstudy participation. A female of childbearing potential (FCBP) is a sexually maturewoman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) hasnot been naturally postmenopausal for at least 24 consecutive months (i.e., has hadmenses at any time in the preceding 24 consecutive months

Exclusion Criteria:

• 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 confidentthat clinical deterioration is a direct result of tumor progression, and could bedue to intercurrent illness

• Persons with edema which might be due to late radiation effect, not trueprogression, should receive bevacizumab as standard of care, and defer studyparticipation. If (short-term) followup imaging shows reduction of edema and alsoprogression of tumor, these persons are eligible (and should continue bevacizumab)

• Pregnant or breast-feeding women will not be entered on this study

• Participants may not have any baseline comorbidities or laboratory abnormalitieswhich would be of grade 3 or worse if graded as toxicities by Common TerminologyCriteria for Adverse Events (CTCAE) (excepting alopecia). An exception is made forneurologic comorbidities (e.g. ataxia, aphasia) arising as a consequence of thebrain tumor; symptoms severe enough to warrant medical treatment as is offered onthis study are by definition grade III

• Persons who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study are ineligible

• Illness or any other circumstances (as defined by the investigator), which wouldpreclude safe performance of study procedures or compromise the ability of thepatient to consent to study

• Persons with hereditary porphyria are ineligible