glioblastoma MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Olaptesed pegol
Product Code: NOX-A12
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OLAPTESED PEGOL
CAS Number: 1390628-22-4
Current Sponsor code: NOX-A
Sponsors
NOXXON Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Criteria for inclusion - 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 (e.g., MGMT promotor 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. Status post biopsy or incomplete resection (detectable residual tumor as per postoperative T1-weighted, contrast-enhanced MRI scan) 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 Criteria for inclusion - 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) or complete resection (Arm A) OR b) Status post complete resection (Arm B) OR c) Status post complete or incomplete resection (circumscribed enhancing tumor = 5.0 cm in largest diameter as per postoperative T1-weighted, contrast-enhanced MRI scan) (Arm C) 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, 4 months Arm C) following last dose of dr
Exclusion criteria
Exclusion criteria: All patients • Cytostatic therapy (chemotherapy) within the past 5 years • 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) • Prior radiotherapy to the head • Any other previous or concomitant experimental glioblastoma treatments • Placement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles • 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, 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 • Treatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma Dose Escalation Cohorts • 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 470 ms), Uncontrolled hypertension (blood pressure = 160/95 mmHg), Heart rate 470 ms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To explore the efficacy of olaptesed pegol in combination with radiation therapy on patients with glioblastoma - To investigate the efficacy of olaptesed pegol in combination with radiation therapy and bevacizumab or pembrolizumab in patients with glioblastoma of unmethylated MGMT promoter status - To investigate the pharmacokinetics of olaptesed pegol during continuous administration - To monitor symptoms (NANO) and Quality of Life;Main Objective: To investigate the safety of either olaptesed pegol in combination with radiation therapy or olaptesed pegol combination with radiation therapy and bevacizumab or pembrolizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status.;Primary end point(s): Safety: Adverse Events;Timepoint(s) of evaluation of this end point: At the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression Free Survival (PFS) at 6 months (PFS-6) • Median progression-free survival (mPFS) • Median overall survival (mOS) • Tumor vascularisation as per vascular MRI scans at baseline and following 2, 4, and 6 months • Topography of recurrence • Determination of maximum tolerated dose (MTD) • Definition of recommended Phase 2 dose (RP2D) • Olaptesed pegol plasma levels at steady state • Neurologic Assessment in Neuro-Oncology (NANO) assessment • Quality of Life;Timepoint(s) of evaluation of this end point: At the end of the study. | — |
Countries
Germany
Contacts
Public ContactClin. Trial Disclosure Desk NOXXON
NOXXON Pharma AG
Outcome results
None listed