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

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NOXXON Pharma AG
• Treatments: Bevacizumab

Criteria

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