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Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Glioblastoma at First Recurrence or Progression

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Medicenna Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Medicenna Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02858895
First received: July 28, 2016
Last updated: May 15, 2017
Last verified: April 2017
  Purpose
This is a single-arm, open-label, multicenter study in approximately 43 adults with primary (de novo) Glioblastoma that has recurred or progressed after failure of first-line therapy [according to Response Assessment in Neuro-Oncology (RANO) criteria]. Eligible subjects will receive intratumoral infusion of MDNA55 administered via convection-enhanced delivery (CED).

Condition Intervention Phase
Glioblastoma
Grade IV Astrocytoma
Glioblastoma Multiforme
Drug: MDNA55
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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 Glioblastoma at First Recurrence or Progression

Resource links provided by NLM:


Further study details as provided by Medicenna Therapeutics, Inc.:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: 12 months ]
    ORR, determined by independent blinded review


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

  • Progression Free Survival (PFS) [ Time Frame: 12 months ]
    PFS, time from treatment until disease progression or death


Other Outcome Measures:
  • Duration of response (DOR) [ Time Frame: 12 months ]
    DOR, time from treatment until disease progression or death among those subjects achieving a complete response (CR) or partial response (PR) to treatment

  • Duration of clinical benefit (DOCB) [ Time Frame: 12 months ]
    DOCB, time from treatment until disease progression or death among those subjects achieving a complete response (CR), partial response (PR), or stable disease (SD)

  • Serious adverse events (SAEs) [ Time Frame: 12 months ]
    Incidence of SAEs

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

  • Electrocardiogram (ECG) [ Time Frame: 0-2 days ]
    Incidence of clinically significant ECG findings

  • Karnofsky Performance Score (KPS) [ Time Frame: 12 months ]
    Changes since baseline

  • Detection of MDNA55 in serum [ Time Frame: 14 days ]
    Serum samples will be collected to determine levels of MDNA55 in serum

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

  • Neutralizing antibody titer [ Time Frame: 12 months ]
    If presence of anti-MDNA55 antibody is found in any sample analyzed, further immunogenicity assessments will be carried out for determination of antibody neutralization potential


Estimated Enrollment: 43
Study Start Date: October 2016
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MDNA55
Single infusion of MDNA55 at a fixed concentration of 1.5 μg/mL. Administration will employ convection enhanced delivery (CED).
Drug: MDNA55
Other Names:
  • IL4-PE
  • Interleukin-4 Pseudomonas Exotoxin
  • Interleukin-4 Pseudomonas Toxin
  • IL4 Pseudomonas Exotoxin
  • NBI-3001
  • cpIL4-PE

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 target, IL4R, is an ideal but under-exploited target for the development of cancer therapeutics, as it is frequently and intensely expressed on a wide variety of human carcinomas. Expression levels of IL4R are low on the surface of healthy and normal cells, but increase several-fold on cancer cells. A majority of cancer biopsy and autopsy samples from adult and pediatric brain tumors, including recurrent glioblastoma biopsies, have been shown to over-express the IL4R. Cells that do not express the IL4R biomarker do not bind to MDNA55 and are, therefore, not subject to PE-mediated effects.

This is a single-arm, open-label, multicenter study in approximately 43 adults with primary (de novo) Glioblastoma that has recurred or progressed after failure of standard first-line therapy (according to RANO criteria). 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 will be performed 14 days after CED infusion. Thereafter, efficacy and safety assessments will be performed at 30, 60, 120, 180, 270, and 360 days after CED infusion. Subjects who discontinue before the Day 360 visit will undergo all the procedures scheduled for the Day 360 visit at the time of discontinuation.

  Eligibility

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

Inclusion Criteria:

  1. ≥ 18 years old, have access to archival tissue from first diagnosis of Glioblastoma and have a life expectancy ≥ 12 weeks
  2. Histologically proven, primary (de novo) Glioblastoma that has recurred or progressed after only 1 standard treatment regimen including surgery and radiotherapy with or without chemotherapy (according to local practice; Stupp protocol, Stupp et al., 2005)
  3. Subjects must have evidence of first tumor recurrence/progression as determined by standard RANO criteria:

    1. Includes primary Glioblastoma
    2. Screening MRI must be performed within 14 days prior to enrollment, and subjects receiving steroids must be on a stable, or decreasing dose for at least 5 days prior to imaging
    3. More than 12 weeks must have elapsed since the completion of radiation therapy at the time of study entry
  4. Recurrent tumor must be a solid, supratentorial, contrast-enhancing Glioblastoma no smaller than 1 cm and no larger than 4 cm in diameter as assessed by the Imaging Core Laboratory based on MRI taken within 14 days prior to catheter placement
  5. If temozolomide was received as part of first line therapy, subjects must have recovered from the toxic effects of temozolomide and be at least 23 days from last dose prior to start of CED infusion
  6. Karnofsky Performance Score (KPS) ≥ 70
  7. Women of child-bearing potential must have a negative beta-human chorionic gonadotropin pregnancy test documented within 14 days prior to treatment
  8. Women and men of child-bearing potential must agree to use adequate contraception; hormonal or barrier method of birth control; abstinence, etc. for the duration of study participation and for 6 months post drug administration. 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
  9. Requirements for organ and marrow function as follows:

    • adequate bone marrow function: leukocytes > 2,000/μL; absolute neutrophil count > 1,000/μL; platelets > 100,000/μL
    • adequate hepatic function: total bilirubin within normal institutional limits; aspartate transaminase (AST) < 2.5 X institutional upper limit of normal (ULN); alanine transaminase (ALT) < 2.5 X institutional ULN
    • adequate renal function: creatinine not to exceed 1.5 × institutional ULN or creatinine clearance: ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional ULN
    • lymphocytes > 500/μL
    • adequate coagulation function: international normalized ratio (INR) < 1.4; partial thromboplastin time (PTT) ≤ institutional ULN, unless receiving therapeutic low molecular weight heparin
  10. Able to read, understand, and sign the informed consent document before undergoing any study-specific procedures or have a legal representative willing to do so; subjects must be registered prior to treatment with study drug
  11. Subjects must be able and willing to undergo multiple brain MRI examinations
  12. Subjects must be able and willing to comply with all study procedures

Exclusion Criteria:

  1. Any prior therapy for Glioblastoma other than that which is considered standard of care for primary Glioblastoma, including but not limited to the following:

    • more than one line of adjuvant temozolomide; temozolomide treatment must have been completed at least 23 days prior to CED infusion
    • prior treatment with another investigational drug
    • prior treatment with bevacizumab (Avastin) or other vascular-endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors
    • prior treatment with nitrosoureas
    • prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants)
  2. Secondary Glioblastoma (i.e., Glioblastoma that progressed from low-grade diffuse astrocytoma or AA)
  3. Unable to provide archival tissue from first diagnosis of Glioblastoma
  4. Tumor in the brain stem (not including fluid-attenuated inversion recovery [FLAIR] changes), an infratentorial tumor, or multifocal satellite tumors
  5. Tumor with a clinically significant mass effect (> 5 mm midline shift) while on a stable corticosteroid dose
  6. Subjects with tumors that are completely liquefied (> 95% cyst) in which convection would not be possible
  7. Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters; these tumors include the following:

    • tumors that appear to wrap around ventricular structures, such that the catheter tips may be positioned > 1.0 cm of a ventricle or such that a large angle (such as an "elbow" or "L- shape") in the tumor shape is present and convection is likely to be compromised
    • tumors in which post-surgical enhancement in T1 images in the margins around a resection cavity may be confused with recurring tumor; subjects in whom this enhancement exceeds 1 cm thickness are excluded
  8. Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
  9. Significant heart disease that precludes the administration of anesthesia
  10. Known to be human immunodeficiency virus positive
  11. On-going treatment with cytotoxic therapy; no additional antineoplastic therapies are planned until there is evidence of tumor progression after administration of the study drug
  12. 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
  13. Known history of allergy to gadolinium contrast agents
  14. Presence of another type of malignancy 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
  15. Unwilling or unable to comply with the requirements of the protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's returning for follow-up visits or other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject's enrollment incompatible with study objectives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02858895

Locations
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Nurse Line    415-353-2652      
Principal Investigator: Nicholas Butowski, MD         
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   
Principal Investigator: Achal Achrol, MD         
United States, Florida
Boca Raton Regional Hospital Recruiting
Boca Raton, Florida, United States, 33486
Contact: Pilar Zuniga, MD    561-955-4800    pzuniga@brrh.com   
Principal Investigator: Frank Vrionis, MD         
United States, New York
Weill Cornell Medical Center - New York Presbyterian Not yet 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   
Principal Investigator: Mark Souweidane, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Brain Tumor Center    919-684-5301      
Principal Investigator: Dina Randazzo, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Terese Wheeler    216-444-0437    wheelet@ccf.org   
Principal Investigator: Michael Vogelbaum, MD, PhD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Barb Kleiber    614-293-1815    Barbara.Kleiber@osumc.edu   
Principal Investigator: Russell Lonser, MD         
United States, Texas
University of Texas Southwestern Cancer Center Recruiting
Dallas, Texas, United States, 75390
Contact: Rafael Leon    214-648-1929    Rafael.leon@utsouthwestern.edu   
Principal Investigator: Toral Patel, MD         
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   
Principal Investigator: Andrew Brenner, MD         
Sponsors and Collaborators
Medicenna Therapeutics, Inc.
  More Information

Additional Information:
Responsible Party: Medicenna Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02858895     History of Changes
Other Study ID Numbers: MDNA55-05
Study First Received: July 28, 2016
Last Updated: May 15, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Medicenna Therapeutics, Inc.:
High grade glioma
malignant glioma
recurrent glioblastoma
recurrent GBM
recurrent GB
glioblastoma (GB)
glioblastoma multiforme (GBM)
progressive glioblastoma

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

ClinicalTrials.gov processed this record on May 25, 2017