Clinical Trials /

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

NCT04590664

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Verteporfin for the Treatment of Recurrent High Grade EGFR-Mutated Glioblastoma
  • Official Title: A Phase 1 / 2 Study of Visudyne (Liposomal Verteporfin) in Persons With Recurrent High Grade EGFR-Mutated Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: STUDY00000974
  • SECONDARY ID: NCI-2020-05187
  • SECONDARY ID: WINSHIP5070-20
  • SECONDARY ID: P30CA138292
  • NCT ID: NCT04590664

Conditions

  • Glioblastoma
  • Recurrent Glioblastoma

Interventions

DrugSynonymsArms
VerteporfinBenzoporphyrin Derivative Monoacid Ring A, BPD-MA, VisudyneTreatment (verteporfin)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (verteporfin)ExperimentalPatients 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

Eligibility Criteria

        Inclusion Criteria:

          -  Persons with recurrent or progressive grade 4 glioma (glioblastoma) are eligible for
             this study. Participants should have received standard first line therapy including
             radiation and temozolomide

          -  Eligible participants have tumors that show mutant or amplified EGFR. This
             determination 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) of
             progression. This may be as new or increased enhancement, or growth / increase in
             nonenhancing abnormality. Care should be taken to distinguish those with true
             progression from those with radiation related changes. Persons with changes in
             enhancement possibly due in part or in whole to late radiation effect should receive
             bevacizumab as standard of care, and defer study participation

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

          -  Visudyne is a vesicant. Participants will likely have poor veins, and will require
             repeated intravenous treatments. Participants must be willing to have placed a central
             venous access, such as a portacath

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3. Participants
             who are ECOG 2 or 3 should ideally have been in that situation for some time, and not
             be in the midst of rapid clinical decline

          -  Medical comorbidities (excepting neurological) must be grade 2 or less if graded as
             toxicity

          -  Eligible participants may have grade 3 neurologic comorbidities (for example aphasia,
             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 include chemotherapy
             and non-bevacizumab therapies. 7 days must have elapsed since discontinuation 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. Radiation
             must 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 are
             unknown. For this reason, female of child-bearing potential (FCBP) must have a
             negative serum or urine pregnancy test prior to starting therapy

          -  FCBP and men must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to study entry and for the duration of study
             participation and 8 weeks after. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation. A female of childbearing potential (FCBP) is a sexually mature woman
             who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
             naturally postmenopausal for at least 24 consecutive months (i.e., has had menses 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 confident
             that clinical deterioration is a direct result of tumor progression, and could be due
             to intercurrent illness

          -  Persons with edema which might be due to late radiation effect, not true progression,
             should receive bevacizumab as standard of care, and defer study participation. If
             (short-term) followup imaging shows reduction of edema and also progression 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 abnormalities which
             would be of grade 3 or worse if graded as toxicities by Common Terminology Criteria
             for Adverse Events (CTCAE) (excepting alopecia). An exception is made for neurologic
             comorbidities (e.g. ataxia, aphasia) arising as a consequence of the brain tumor;
             symptoms severe enough to warrant medical treatment as is offered on this study are by
             definition grade III

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

          -  Illness or any other circumstances (as defined by the investigator), which would
             preclude safe performance of study procedures or compromise the ability of the patient
             to consent to study

          -  Persons with hereditary porphyria are ineligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (Phase I)
Time Frame:From study enrollment until 100 days after the last day of study participation
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:PFS (Phase I)
Time Frame:From study enrollment to 2 years
Safety Issue:
Description:Will be assessed by RANO for MRI of glioblastoma.
Measure:RR (Phase I)
Time Frame:From study enrollment to 2 years
Safety Issue:
Description:Will be assessed by RANO for MRI of glioblastoma. Response rate will be estimated, and a 95% confidence interval will be estimated using the Clopper-Pearson method.
Measure:Overall survival (Phase I)
Time Frame:Time from study enrollment to death or last follow-up, assessed up to 2 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Visudyne blood levels (Phase I)
Time Frame:At timepoints following administration
Safety Issue:
Description:Will be summarized descriptively using mean, median, standard deviation, and range at each time point.
Measure:Incidence of adverse events (Phase II)
Time Frame:From study enrollment to 2 years
Safety Issue:
Description:Will be graded by NCI CTCAE version 5.0.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

Last Updated

October 11, 2020