Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Nicholas Butowski

Description

Summary

This is a single-arm, open-label, multicenter study in approximately 52 adults with primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence) after treatment(s) including surgery and radiotherapy with or without chemotherapy and following discontinuation of any previous standard or investigational lines of therapy.

Official Title

An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Details

The study drug, MDNA55, is a fusion protein comprising a genetically engineered Interleukin-4 (IL-4) linked to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE.

The study will be conducted at up to 10 clinical sites following institutional review board approval and completed informed consent.

Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will be administered locally by convection-enhanced delivery (CED).

Post-treatment follow-up assessment of safety and efficacy will be performed monthly for the first 6 months and bimonthly thereafter for approximately 1 year after study drug administrations. Subjects will continued to be followed for survival and post-study treatment(s) of GB after study completion or withdrawal.

Keywords

Glioblastoma Grade IV Astrocytoma Glioblastoma Multiforme Grade IV Glioma High grade glioma malignant glioma recurrent glioblastoma recurrent GBM recurrent GB glioblastoma (GB) glioblastoma multiforme (GBM) progressive glioblastoma Brain tumor Brain cancer immunotherapy targeted IL4R Glioma Astrocytoma Interleukin-4 MDNA55

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks
  2. Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence)
  3. Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis
  4. Recurrent tumor must be supratentorial, contrast-enhancing GB no smaller than 1 cm x 1 cm (largest perpendicular dimensions) and no larger than 4 cm maximum in a single direction based on MRI taken within 14 days prior to catheter placement
  5. Karnofsky Performance Score (KPS) ≥ 70
  6. Subjects must be able and willing to undergo multiple brain MRI examinations
  7. Subjects must be able and willing to comply with all study procedures
  8. Any related toxicities following discontinuation of prior GB therapies must have resolved to CTCAE Grade 1 or lower prior to inclusion in this study

You CAN'T join if...

  1. Prior treatment with cytotoxic chemotherapy
  2. Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion
  3. "Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion
  4. Nitrosoureas within the past 6 weeks prior to planned infusion
  5. Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion
  6. Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion
  7. Prior treatment with bevacizumab (Avastin) or other vascular-endothelial growth factor(VEGF) inhibitors or VEGF-receptor signaling inhibitors within the past 4 weeks prior to planned infusion
  8. Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
  9. Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion
  10. Ongoing Optune© therapy within 5 days of planned infusion
  11. Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA)
  12. Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene.
  13. Tumor in the brainstem (not including fluid-attenuated inversion recovery [FLAIR]changes), an infratentorial tumor, diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense tumor with ill-defined margins encompassing at least three lobes of the brain.
  14. . Tumor with a mass effect (e.g. 1-2 cm midline shift)
  15. . Subjects with tumors for which the preponderance of tissue is not of the type in which convection would be possible (e.g. preponderance of cystic component)
  16. . Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters
  17. . Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
  18. . Any condition that precludes the administration of anesthesia
  19. . Known to be human immunodeficiency virus positive
  20. . Concurrent or a history of any significant medical illnesses that in the Investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the subject's ability to tolerate the study drug therapy and/or put the subject at additional risk or interfere with the interpretation of the results of this trial
  21. . Known history of allergy to gadolinium contrast agents
  22. . Presence of another type of malignancy requiring treatment within < 3 years prior to the screening visit, except for adequately treated carcinoma in-situ of the cervix,prostate cancer not actively treated, and basal or squamous cell carcinoma of the skin

Locations

  • University of California San Francisco accepting new patients
    San Francisco California 94143 United States
  • John Wayne Cancer Institute at Providence Saint John's Health Center accepting new patients
    Santa Monica California 90404 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Medicenna Therapeutics, Inc.
Links
Sponsor website
ID
NCT02858895
Phase
Phase 2
Lead Scientist
Nicholas Butowski
Study Type
Interventional
Last Updated
August 8, 2018