Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent Glioblastoma (GBM)

Phase 2/3

Suspended

• Conditions: Oncology - Glioblastoma (GBM)

• Registration Number: 2024-511452-40-00
• Lead Sponsor: Global Coalition For Adaptive Research Inc.

Brief Summary

1. To identify experimental therapies that improve overall survival (OS) for GBM patients in the Screening stage (Stage 1), determining if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment

2. To confirm identified efficacious experimental therapies and associated biomarker signatures in an expansion stage (Stage 2) designed to support a new drug application

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-16
• Last Update Posted: 2024-07-17

Recruitment & Eligibility

• Status: Temporarily halted
• Sex: Not specified
• Target Recruitment: 80

Inclusion Criteria

All patients: Age ≥ 18 years

Recurrent: Baseline MRI performed within 14 days prior to randomization

Recurrent: Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization

Recurrent: Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Newly Diagnosed: Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. A diagnosis made based on molecular characteristics alone is not allowed

Newly Diagnosed: An MRI scan performed within 21 days prior to randomization preferably

Newly Diagnosed: Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization

Newly Diagnosed: Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization

Newly Diagnosed: Availability of tumor tissue representative of GBM from definitive surgery or biopsy.

Recurrent: Histologically confirmed GBM, inclusive of gliosarcoma (WHO criteria 2016; IDH wild-type) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum Radiation Therapy (RT). (prior therapy with proton radiation or short course radiation is acceptable)

Recurrent: Evidence of recurrent disease (RD) demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria

Recurrent: Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization

Exclusion Criteria

Newly Diagnosed: Any prior treatment for glioma including: prior prolifeprospan 20 with carmustine wafer; prior intracerebral agent; intratumoral, or cerebral spinal fluid (CSF) agent; prior radiation treatment (including proton radiation and short course radiation) for GBM or lower-grade glioma; prior chemotherapy or immunotherapy for GBM or lower-grade glioma

Newly Diagnosed: QTc > 450 msec if male and QTc > 470 msec if female

Newly Diagnosed: History of another malignancy in the previous 2 years, with a diseasefree interval of < 2 years. Note: Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible

Recurrent: Early disease progression prior to 3 months (12 weeks) from the completion of RT

Recurrent: More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of Temozolomide (TMZ) with an experimental agent is considered one line of chemotherapy)

Recurrent: Any prior treatment with lomustine, experimental agents currently enrolling in the GBM AGILE trial, and bevacizumab or other VEGF)- or VEGF receptor-mediated targeted agent

Recurrent: Any prior treatment with prolifeprospan 20 with carmustine wafer

Recurrent: Any prior treatment with an intracerebral agent

Recurrent: Receiving additional, concurrent, active therapy (including experimental) for GBM outside of the trial

Recurrent: Extensive leptomeningeal disease

Recurrent: QTc > 450 msec if male and QTc > 470 msec if female

Recurrent: History of another malignancy in the previous 2 years, with a diseasefree interval of < 2 years. Note: Participants with prior history of in situ cancer or basal or squamous cell skin cancer are eligible

Newly Diagnosed: Receiving additional, concurrent, active therapy (including experimental) for GBM outside of the trial

Newly Diagnosed: Extensive leptomeningeal disease Leptomeningeal disease in the region of the primary tumor and confined to the supratentorial area is allowed

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Overall Survival defined from the time of randomization to death from any cause		Overall Survival defined from the time of randomization to death from any cause

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival defined as the time from randomization to clinically determined progression or death from any cause		Progression-Free Survival defined as the time from randomization to clinically determined progression or death from any cause
Tumor Response: complete response, partial response, progressive disease, stable disease		Tumor Response: complete response, partial response, progressive disease, stable disease
Duration of Response: - Complete Response and Partial Response defined as time from date of response to date of clinically determined disease progression or death from any cause		Duration of Response: - Complete Response and Partial Response defined as time from date of response to date of clinically determined disease progression or death from any cause

Trial Locations

Locations (10)

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Regional De Marseille; 🇫🇷 Marseille, France

Hospital Pierre Wertheimer; 🇫🇷 Bron, France

Universitaetsklinikum Regensburg AöR; 🇩🇪 Regensburg, Germany

Universitaetsklinikum Bonn AöR; 🇩🇪 Bonn, Germany

University Hospital Cologne AöR; 🇩🇪 Cologne, Germany

Goethe University Frankfurt; 🇩🇪 Frankfurt Am Main, Germany

Universitaetsklinikum Heidelberg AöR; 🇩🇪 Heidelberg, Germany

Universitat Heidelberg; 🇩🇪 Mannheim, Germany

Universitaetsklinikum Tuebingen AöR; 🇩🇪 Tuebingen, Germany

Assistance Publique Hopitaux De Paris

🇫🇷Paris, France

Antoine CARPENTIER

Site contact

+33171207466

antoine.carpentier@aphp.fr

Mehdi TOUAT

Site contact

+33142160381

mehdi.touat@aphp.fr