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Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients (GLORIA)

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ClinicalTrials.gov Identifier: NCT04121455
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
NOXXON Pharma AG

Tracking Information
First Submitted Date  ICMJE September 25, 2019
First Posted Date  ICMJE October 10, 2019
Last Update Posted Date November 5, 2021
Actual Study Start Date  ICMJE September 12, 2019
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
Safety - Number of patients with treatment-related adverse events as assessed by CTCAE [ Time Frame: 26 weeks ]
Number of patients with treatment-related adverse events as assessed by CTCAE
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Efficacy - progression free survival at 6 months (PFS-6) [ Time Frame: 6 months ]
    Progression free survival at 6 months (PFS-6) in %
  • Efficacy - Median progression-free survival (mPFS) [ Time Frame: 24 months ]
    Median progression-free survival (mPFS) in months
  • Efficacy - Median overall survival (mOS) [ Time Frame: 24 months ]
    Median overall survival (mOS) in months
  • Efficacy - Tumor vascularization as per vascular MRI [ Time Frame: 24 months ]
    Changes from baseline in tumor vascularization over time as %cerebral blood volume
  • Plasma level of olaptesed pegol [ Time Frame: 26 weeks ]
    concentration of olaptesed pegol in plasma in µmol/L
  • Quality of Life (QoL) EORTC QLQ-C30 Module [ Time Frame: 24 months ]
    Quality of Life measures are recorded according to EORTC QLQ30 module, which is validated for cancer patients in general and measured as a unit of scale. This is a standard tool for assessing patient reported quality of Life along time during treatment.
  • Quality of Life (QoL) EORTC QLQ BN-20 Module [ Time Frame: 24 months ]
    Quality of Life measures are recorded according to EORTC QLQ BN-20 module, which is validated for brain tumor patients and measured as a unit of scale. This is a standard tool for assessing patient reported quality of Life along time during treatment.
  • Neurologic functions as measured by the NANO scale [ Time Frame: 24 months ]
    Change from baseline in neurologic performance scores by Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The NANO Scale evaluates 9 major domains of neurologic function, with each domain being scored on a range from 0 to 2 or 3.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients
Official Title  ICMJE Single-arm Dose-escalation Phase 1/2 Study of Olaptesed Pegol (NOX-A12) in Combination With Irradiation in Inoperable or Partially Resected First-line Glioblastoma Patients With Unmethylated MGMT Promoter With a 2-arm Expansion Group Including Fully Resected Patients and Combination With Bevacizumab
Brief Summary The purpose of this study is to obtain first, exploratory information on the safety and efficacy of (i) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete tumor resection, (ii) olaptesed pegol in combination with radiation therapy and bevacizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete tumor resection and (iii) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after complete tumor resection.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 dose escalation and a 2-arm expansion group
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: Olaptesed pegol
    Olaptesed pegol continuous administration for 26 weeks
  • Radiation: Radiotherapy
    Radiotherapy in weeks 1-6; cumulative dose of 60 Gy in 2 Gy fractions
  • Drug: Bevacizumab
    Bevacizumab every 2 weeks i.v. for 26 weeks
    Other Name: MVASI
Study Arms  ICMJE
  • Experimental: Cohort 1: 200 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
    Interventions:
    • Drug: Olaptesed pegol
    • Radiation: Radiotherapy
  • Experimental: Cohort 2: 400 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
    Interventions:
    • Drug: Olaptesed pegol
    • Radiation: Radiotherapy
  • Experimental: Cohort 3: 600 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
    Interventions:
    • Drug: Olaptesed pegol
    • Radiation: Radiotherapy
  • Experimental: Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients
    Interventions:
    • Drug: Olaptesed pegol
    • Radiation: Radiotherapy
    • Drug: Bevacizumab
  • Experimental: Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
    Interventions:
    • Drug: Olaptesed pegol
    • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2021)
21
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2019)
9
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria Dose Escalation Cohorts:

  1. Written informed consent
  2. Age ≥18 years
  3. Patient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy
  4. Patient agrees to subcutaneous port implantation
  5. Newly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma
  6. Status post biopsy or incomplete resection
  7. Unmethylated MGMT promoter status
  8. Maximum Eastern Cooperative Oncology Group (ECOG) score 2
  9. Estimated minimum life expectancy 3 months
  10. Stable or decreasing dose of corticosteroids during the week prior to inclusion
  11. The following laboratory parameters should be within the ranges specified:

    • Total bilirubin ≤ 1.5 x upper limit normal (ULN)
    • Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m²
    • ALT (alanine transaminase) ≤ 3 x ULN
    • AST (aspartate transaminase) ≤ 3 x ULN
  12. Female patients of child-bearing potential must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly such as contraceptive implants, vaginal rings, sterilization, or sexual abstinence)" during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)
  13. Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP

Inclusion Criteria Expansion Group:

  1. Written informed consent
  2. Age ≥ 18 years
  3. Patient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy (e.g., MGMT promoter analysis, cytogenetic markers such as IDH-1 mutations, etc.)
  4. Patient agrees to subcutaneous port implantation
  5. Newly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma
  6. a) Status post biopsy or incomplete resection (detectable residual tumor as per postoperative T1-weighted, contrast-enhanced MRI scan) (Arm A) OR b) Status post complete resection (Arm B)
  7. Unmethylated MGMT promoter status
  8. Maximum Eastern Cooperative Oncology Group (ECOG) score 2
  9. Estimated minimum life expectancy 3 months
  10. Stable or decreasing dose of corticosteroids during the week prior to inclusion
  11. The following laboratory parameters should be within the ranges specified:

    • Total bilirubin ≤ 1.5 x upper limit normal (ULN)
    • Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m²
    • ALT (alanine transaminase) ≤ 3 x ULN
    • AST (aspartate transaminase) ≤ 3 x ULN
  12. Female patients of child-bearing potential must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly such as contraceptive implants, vaginal rings, sterilization, or sexual abstinence) during and for 3 months (6 months Arm A) following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)
  13. Male patients must use an effective barrier method of contraception during study and for 3 months (6 months Arm A) following the last dose if sexually active with a FCBP

Exclusion Criteria Dose Escalation Cohorts:

  1. Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements
  2. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days from screening visit or observation period of competing studies
  3. Contra-indication or known hypersensitivity to MRI contrast agents, olaptesed pegol or polyethylene glycol
  4. Cytostatic therapy (chemotherapy) within the past 5 years
  5. History of other cancers (except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient was disease-free for ≥ 5 years)
  6. Clinically significant or uncontrolled cardiovascular disease
  7. Prior radiotherapy to the head
  8. Any other previous or concomitant experimental glioblastoma treatments
  9. Placement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles
  10. Pregnancy or lactation
  11. Uncontrolled intercurrent illness; patients must be free of any clinically relevant disease (other than glioma) that would, in the treating investigator's opinion, interfere with the conduct of the study or study evaluations
  12. Treatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma
  13. Prior enrolment into this study

Exclusion Criteria Expansion Group:

  1. Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements
  2. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days from screening visit or observation period of competing studies
  3. Contra-indication or known hypersensitivity to MRI contrast agents, bevacizumab (Arm A only) olaptesed pegol or polyethylene glycol
  4. Planned hypofractionated radiotherapy
  5. Cytostatic therapy (chemotherapy) within the past 5 years
  6. History of other cancers (except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient was disease-free for ≥ 5 years)
  7. Secondary malignancy which is currently active
  8. Clinically significant or uncontrolled cardiovascular disease, including

    • Myocardial infarction in the previous 12 months
    • Uncontrolled angina
    • Congestive heart failure (New York Heart Association functional classification of ≥2)
    • Diagnosed or suspected congenital long QT syndrome
    • QTc prolongation on an electrocardiogram prior to entry (>470 ms)
    • Uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)
    • Heart rate <50/min on the baseline electrocardiogram
    • History of ventricular arrhythmias of any clinically significant type (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes)
    • Cerebrovascular accident
  9. Prior radiotherapy to the head
  10. Any other previous or concomitant experimental glioblastoma treatments
  11. Placement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles
  12. Patients with a history of arterial or venous thrombosis (or any other disease) requiring permanent intake of anticoagulants (Arm A only)
  13. Pregnancy or lactation
  14. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease (e.g., cirrhosis, hepatitis), diabetes mellitus, or subjects with either of the following: fasting blood glucose (FBG defined as fasting for at least 8 hours) ≥ 200 mg/dL (7.0 mmol/L), or HbA1c ≥ 8%, chronic renal disease, pancreatitis, chronic pulmonary disease, auto-immune diseases, or psychiatric illness/social situations that would limit compliance with study requirements. Patients must be free of any clinically relevant disease (other than glioma) that would, in the treating investigator's opinion, interfere with the conduct of the study or study evaluations
  15. Prolongation of coagulation factors ≥ 2.5 x ULN (Arm A only)
  16. Treatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma
  17. Prior enrolment into this study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Diana Beyer, Dr. +49 30 72 62 47 ext 100 clinicaltrialdisclosuredesk@noxxon.com
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04121455
Other Study ID Numbers  ICMJE SNOXA12C401
2018-004064-62 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NOXXON Pharma AG
Study Sponsor  ICMJE NOXXON Pharma AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account NOXXON Pharma AG
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP