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Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

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ClinicalTrials.gov Identifier: NCT02858895
Recruitment Status : Recruiting
First Posted : August 8, 2016
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Medicenna Therapeutics, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Glioblastoma Grade IV Astrocytoma Glioblastoma Multiforme Grade IV Glioma Drug: MDNA55 Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MDNA55

Single infusion of MDNA55 via convection enhanced delivery (CED).*

*Subjects may be eligible to receive a second administration of MDNA55.

Drug: MDNA55
Other Names:
  • IL4-PE
  • Interleukin-4 Pseudomonas Exotoxin
  • Interleukin-4 Pseudomonas Toxin
  • IL4 Pseudomonas Exotoxin
  • NBI-3001
  • cpIL4-PE




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 12 months ]
    ORR, determined by independent central review (per RANO-based criteria)


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 12 months ]
    OS, time from treatment until death

  2. Progression Free Survival (PFS) [ Time Frame: 12 months ]
    PFS, time from treatment until disease progression (per RANO-based criteria) or death


Other Outcome Measures:
  1. Serious adverse events (SAEs) [ Time Frame: 12 months ]
    Incidence of SAEs

  2. Treatment emergent adverse events (AEs) [ Time Frame: 12 months ]
    Incidence of Treatment-Emergent AEs

  3. Pharmacokinetics (PK) of MDNA55 [ Time Frame: 14 days ]
    Blood samples will be collected to determine levels of MDNA55

  4. Anti-MDNA55 antibody [ Time Frame: 12 months ]
    Blood samples will be collected to determine anti-drug antibody titers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  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

EXCLUSION CRITERIA:

  1. Prior treatment with cytotoxic chemotherapy

    1. Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion
    2. "Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion
    3. Nitrosoureas within the past 6 weeks prior to planned infusion
    4. Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion
  2. Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion
  3. 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
  4. Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
  5. Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion
  6. Ongoing Optune© therapy within 5 days of planned infusion
  7. Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA)
  8. Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene.
  9. 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.
  10. Tumor with a mass effect (e.g. 1-2 cm midline shift)
  11. 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)
  12. Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters
  13. Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
  14. Any condition that precludes the administration of anesthesia
  15. Known to be human immunodeficiency virus positive
  16. 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
  17. Known history of allergy to gadolinium contrast agents
  18. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02858895


Contacts
Contact: Nina Merchant 647-346-7867 nmerchant@medicenna.com
Contact: Melissa Coello mcoello@medicenna.com

Locations
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Nurse Line    415-353-2652      
John Wayne Cancer Institute at Providence Saint John's Health Center Recruiting
Santa Monica, California, United States, 90404
Contact: Naj Boucher    310-582-7460    Najee.Boucher@providence.org   
United States, Florida
Boca Raton Regional Hospital Recruiting
Boca Raton, Florida, United States, 33486
Contact: Pilar Zuniga, MD    561-955-4800    pzuniga@brrh.com   
United States, New York
Weill Cornell Medical Center - New York Presbyterian Recruiting
New York, New York, United States, 10022
Contact: Mary O'Hehir    212-746-7373    mao2037@med.cornell.edu   
Contact: Alyson Hignight    212-746-1788    alh2031@med.cornell.edu   
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Brain Tumor Center    919-684-5301      
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Cathy Brewer, RN    216-444-7937    brewerc1@ccf.org   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 3
Contact: Amanda Cole, MS, ACRP    503-494-4988    coleam@ohsu.edu   
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Scott Levy    215-662-6832    Scott.Levy@uphs.upenn.edu   
United States, Texas
Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Epp Goodwin    210-450-5798    CTRC-ReferralCenter@uthscsa.edu   
Poland
Mazovian Brodnowski Hospital Recruiting
Warsaw, Poland, 03-242
Contact: Karolina Karas    +48 600 953 994    k.karas.inc@gmail.com   
Sponsors and Collaborators
Medicenna Therapeutics, Inc.

Additional Information:
Responsible Party: Medicenna Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02858895     History of Changes
Other Study ID Numbers: MDNA55-05
First Posted: August 8, 2016    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Medicenna Therapeutics, Inc.:
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

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Interleukin-4
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents