Glioblastoma treatment with irradiation and olaptesed pegol in unmethylated patients

Phase 1

• Conditions: glioblastoma; MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004064-62-DE
• Lead Sponsor: OXXON Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-08
• Last Update Posted: 21 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 27

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

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 <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)

Arms A and B
• Planned hypofractionated radiotherapy
• Secondary malignancy which is currently active
• 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
• Patients with a history of arterial or venous thrombosis (or any other disease) requiring permanent intake of anticoagulants (Arm A only)
• Prolongation of coagulation factors = 2.5 x ULN (Arm A only)

Arm C
• Biopsy-only of GBM with less than 20% of tumor removed
• Presence of extracranial metastatic or leptomeningeal disease
• Severe hypersensitivity (= Grade 3) to other monoclonal antibodies
• Receiving immunosuppressive therapy
• Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent
• Planned hypofractionated radiotherapy
• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified