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

Phase 1

Active, not recruiting

• Conditions: Glioblastoma
• Interventions: Drug: Olaptesed pegol; Drug: Temozolomide (TMZ); Radiation: Radiotherapy; Drug: Bevacizumab; Drug: Pembrolizumab

• Registration Number: NCT04121455
• Lead Sponsor: TME Pharma AG

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 or complete tumor resection, (iii) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after complete tumor resection, and (iv) olaptesed pegol in combination with radiation therapy and pembrolizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after either complete or incomplete tumor resection.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2019-09-12
• Study First Submitted: 2019-09-25
• Study First Submitted QC: 2019-10-08
• Study First Posted: 2019-10-10
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-20
• Last Update Posted: 2023-06-22
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab	Olaptesed pegol	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Olaptesed pegol	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Olaptesed pegol	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab	Olaptesed pegol	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy	Temozolomide (TMZ)	oral treatment up to 35 weeks according to current SPC
Cohort 2: 400 mg Olaptesed pegol + Radiotherapy	Radiotherapy	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Cohort 3: 600 mg Olaptesed pegol + Radiotherapy	Olaptesed pegol	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Cohort 1: 200 mg Olaptesed pegol + Radiotherapy	Olaptesed pegol	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Cohort 1: 200 mg Olaptesed pegol + Radiotherapy	Radiotherapy	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Cohort 2: 400 mg Olaptesed pegol + Radiotherapy	Olaptesed pegol	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Cohort 3: 600 mg Olaptesed pegol + Radiotherapy	Radiotherapy	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Radiotherapy	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
Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy	Radiotherapy	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab	Radiotherapy	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Radiotherapy	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Radiotherapy	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab	Radiotherapy	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy	Olaptesed pegol	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy	Radiotherapy	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy	Radiotherapy	oral treatment up to 35 weeks according to current SPC
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	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
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Olaptesed pegol	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
Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy	Olaptesed pegol	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab	Pembrolizumab	olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Bevacizumab	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab	Bevacizumab	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab	Bevacizumab	olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients

Primary Outcome Measures

Name	Time	Method
Safety - Number of patients with treatment-related adverse events as assessed by CTCAE	through study completion, an average of 3 years	Number of patients with treatment-related adverse events as assessed by CTCAE

Secondary Outcome Measures

Name	Time	Method
Efficacy - progression free survival at 6 months (PFS-6)	6 months	Progression free survival at 6 months (PFS-6) in %
Efficacy - Median progression-free survival (mPFS)	until end of treatment, an average 1 year	Median progression-free survival (mPFS) in months
Efficacy - Median overall survival (mOS)	through study completion, an average of 3 years	Median overall survival (mOS) in months
Efficacy - Landmark overall survival at 18 months (OS18)	18 months
Overall response rate (ORR)	through study completion, an average of 3 years
Plasma level of olaptesed pegol	9 weeks after treatment start	concentration of olaptesed pegol in plasma in µmol/L
Quality of Life (QoL) EORTC QLQ-C30 Module	through study completion, an average of 3 years	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	through study completion, an average of 3 years	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.
Efficacy - Tumor vascularization as per vascular MRI	through study completion, an average of 3 years	Changes from baseline in tumor vascularization over time as %cerebral blood volume
Neurologic functions as measured by the NANO scale	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.

Trial Locations

Locations (5)

Klinik und Poliklinik für Neurologie Schwerpunkt Klinische Neuroonkologie; 🇩🇪 Bonn, Germany

Klinik für Strahlentherapie und Radioonkologie; 🇩🇪 Mannheim, Germany

Klinik für Neurologie; 🇩🇪 Essen, Germany

Abteilung Neurologie mit interdisziplinärem Schwerpunkt Neuroonkologie; 🇩🇪 Tübingen, Germany

Klinik für Neurologie mit Institut für Translationale Neurologie; 🇩🇪 Münster, Germany