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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Global Coalition For Adaptive Research Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Sep 2025 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Global Coalition for Adaptive Research

External identifiers

EU CT number

2024-511452-40-00

EudraCT number

2020-002250-24

ClinicalTrials.gov

NCT03970447

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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

Secondary objectives 3

1. To evaluate Progression Free Survival (PFS), duration of response, and tumour response by each biomarker/therapeutic combination
2. To evaluate OS by each biomarker/therapeutic combination
3. To determine short- and long-term safety signals and quality of life (QOL) measures of an experimental Arm in GBM patients versus standard of care

Conditions and MedDRA coding

Oncology - Glioblastoma (GBM)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. All patients: Age ≥ 18 years
2. 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
3. Newly Diagnosed: An MRI scan performed within 21 days prior to randomization preferably
4. Newly Diagnosed: Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization
5. Newly Diagnosed: Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization
6. Newly Diagnosed: Availability of tumor tissue representative of GBM from definitive surgery or biopsy.
7. 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)
8. Recurrent: Evidence of recurrent disease (RD) demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria
9. Recurrent: Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization
10. Recurrent: Baseline MRI performed within 14 days prior to randomization
11. Recurrent: Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization
12. Recurrent: Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Exclusion criteria 14

1. 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
2. Recurrent: Any prior treatment with prolifeprospan 20 with carmustine wafer
3. Recurrent: Any prior treatment with an intracerebral agent
4. Recurrent: Receiving additional, concurrent, active therapy (including experimental) for GBM outside of the trial
5. Recurrent: Extensive leptomeningeal disease
6. Recurrent: QTc > 470 msec
7. 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
8. Newly Diagnosed: Receiving additional, concurrent, active therapy (including experimental) for GBM outside of the trial
9. Newly Diagnosed: Extensive leptomeningeal disease Leptomeningeal disease in the region of the primary tumor and confined to the supratentorial area is allowed
10. Newly Diagnosed: QTc > 470 msec
11. 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
12. Recurrent: Early disease progression prior to 3 months (12 weeks) from the completion of RT
13. 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)
14. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival defined from the time of randomization to death from any cause

Secondary endpoints 3

1. Progression-Free Survival defined as the time from randomization to clinically determined progression or death from any cause
2. Tumor Response: complete response, partial response, progressive disease, stable disease
3. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Global Coalition For Adaptive Research Inc.

Sponsor organisation

Global Coalition For Adaptive Research Inc.

Address

700 Larkspur Landing Circle, Suite 199 Suite 199

City

Larkspur

Postcode

94939-1754

Country

United States

Scientific contact point

Organisation

Global Coalition For Adaptive Research Inc.

Contact name

Regulatory Affairs

Public contact point

Organisation

Global Coalition For Adaptive Research Inc.

Contact name

Regulatory Affairs

Third parties 8

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications