search
Back to results

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

Primary Purpose

Glioblastoma, Grade IV Astrocytoma, Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MDNA55
Sponsored by
Medicenna Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Francisco
  • John Wayne Cancer Institute at Providence Saint John's Health Center
  • Boca Raton Regional Hospital
  • Duke University Medical Center
  • Oregon Health & Science University
  • Hospital of the University of Pennsylvania
  • Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MDNA55

Arm Description

Single infusion of MDNA55 via convection enhanced delivery (CED).* *Subjects may be eligible to receive a second administration of MDNA55.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.

Secondary Outcome Measures

Objective Response Rate (ORR)
ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions. Stable Disease - Does not qualify for CR, PR, or PD as defined above
Progression Free Survival (PFS)
PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions

Full Information

First Posted
July 28, 2016
Last Updated
October 18, 2022
Sponsor
Medicenna Therapeutics, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02858895
Brief Title
Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
April 11, 2017 (Actual)
Primary Completion Date
September 12, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medicenna Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Grade IV Astrocytoma, Glioblastoma Multiforme, Grade IV Glioma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MDNA55
Arm Type
Experimental
Arm Description
Single infusion of MDNA55 via convection enhanced delivery (CED).* *Subjects may be eligible to receive a second administration of MDNA55.
Intervention Type
Drug
Intervention Name(s)
MDNA55
Other Intervention Name(s)
IL4-PE, Interleukin-4 Pseudomonas Exotoxin, Interleukin-4 Pseudomonas Toxin, IL4 Pseudomonas Exotoxin, NBI-3001, cpIL4-PE
Intervention Description
MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.
Time Frame
From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions. Stable Disease - Does not qualify for CR, PR, or PD as defined above
Time Frame
12 months
Title
Progression Free Survival (PFS)
Description
PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Number of Subjects With Serious Adverse Events
Description
Number of Subjects with Serious adverse events with Frequency >=5%
Time Frame
12 months
Title
Treatment Emergent Adverse Events
Description
Incidence of Treatment-Emergent adverse events
Time Frame
12 months
Title
Level of MDNA55 in Peripheral Plasma
Description
Systemic exposure to MDNA55 is not expected following intratumoral infusion and circulating MDNA55 has not been detected in previous clinical studies. To continue to evaluate the potential of systemic exposure, plasma collected at screening (baseline), within 1 hour following infusion end time, ~3 hours following completion of infusion and then (after the ~3 hour sample collection) every 6 hours ± 2 hours until 24 hours and at Day 14. PK data will be presented for the PK population in listing format by subject and sample collection time point. PK parameters would only be analyzed if MDNA55 levels above LLOQ (0.37 ng/mL) were detected.
Time Frame
14 days
Title
ADA Titer / Neutralizing Antibody Analysis
Description
Number of participants that were ADA Positive and had Neutralizing Antibody
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence) Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis 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 Karnofsky Performance Score (KPS) ≥ 70 Subjects must be able and willing to undergo multiple brain MRI examinations Subjects must be able and willing to comply with all study procedures 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: Prior treatment with cytotoxic chemotherapy Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion "Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion Nitrosoureas within the past 6 weeks prior to planned infusion Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion 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 Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion Ongoing Optune© therapy within 5 days of planned infusion Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA) Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene. 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. Tumor with a mass effect (e.g. 1-2 cm midline shift) 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) Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain Any condition that precludes the administration of anesthesia Known to be human immunodeficiency virus positive 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 Known history of allergy to gadolinium contrast agents 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
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
John Wayne Cancer Institute at Providence Saint John's Health Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Boca Raton Regional Hospital
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33863808
Citation
Ellingson BM, Sampson J, Achrol AS, Aghi MK, Bankiewicz K, Wang C, Bexon M, Brem S, Brenner A, Chowdhary S, Floyd JR, Han S, Kesari S, Randazzo D, Vogelbaum MA, Vrionis F, Zabek M, Butowski N, Coello M, Merchant N, Merchant F. Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma. Clin Cancer Res. 2021 Jul 15;27(14):3916-3925. doi: 10.1158/1078-0432.CCR-21-0446. Epub 2021 Apr 16.
Results Reference
derived
Links:
URL
http://www.medicenna.com
Description
Sponsor website

Learn more about this trial

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

We'll reach out to this number within 24 hrs