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Evaluating therapies for newly diagnosed and recurrent glioblastoma

GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II/III Response Adaptive Randomization Platform Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent GBM

Phase2; Phase3 Interventional Global Coalition for Adaptive Research · NCT03970447

This study is testing different treatments for people with newly diagnosed or recurring glioblastoma to see which ones work best for different types of the disease.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment2250 (estimated)
Ages18 Years and up
SexAll
SponsorGlobal Coalition for Adaptive Research Academic / other
Drugs / interventionsbevacizumab, chemotherapy, immunotherapy, radiation
Locations63 sites (Birmingham, Alabama and 62 other locations)
Trial IDNCT03970447 on ClinicalTrials.gov

What this trial studies

This trial, known as GBM AGILE, is an international platform designed to evaluate multiple therapies for glioblastoma, both newly diagnosed and recurrent cases. It employs a response adaptive randomization approach, allowing for the assignment of participants to different treatment arms based on their performance and specific disease subtypes. The trial aims to identify effective therapies and match them with patient subtypes, utilizing a single Master Protocol to streamline the evaluation of various drugs and combinations. The primary endpoint of the trial is overall survival.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed Grade IV glioblastoma, either newly diagnosed or recurrent.

Not a fit: Patients with non-Grade IV glioblastoma or those who do not meet the specific inclusion criteria may not benefit from this trial.

Why it matters

Potential benefit: If successful, this trial could lead to more effective treatment options tailored to individual glioblastoma patients, potentially improving survival rates.

How similar studies have performed: Previous studies utilizing adaptive randomization in cancer treatment have shown promise, suggesting that this approach may be effective in identifying beneficial therapies for glioblastoma.

Eligibility criteria

Show full inclusion / exclusion criteria 
Newly Diagnosed Inclusion Criteria:

* Age ≥ 18 years.
* 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. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
* Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from definitive surgery or biopsy.

Recurrent Inclusion Criteria:

* Age ≥ 18 years.
* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \[IHC\] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
* Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
* Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
* Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Newly Diagnosed Exclusion Criteria:

* Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
* Extensive leptomeningeal disease.
* QTc \> 470 msec
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Recurrent Exclusion Criteria:

* Early disease progression prior to 3 months (12 weeks) from the completion of RT.
* 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.)
* Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
* Any prior treatment with prolifeprospan 20 with carmustine wafer.
* Any prior treatment with an intracerebral agent.
* Receiving additional, concurrent, active therapy for GBM outside of the trial
* Extensive leptomeningeal disease.
* QTc \> 470 msec
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Where this trial is running

Birmingham, Alabama and 62 other locations

+13 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GlioblastomaNewly diagnosedrecurrentO6-methylguanine-DNA-methyltransferase methylatedMGMT unmethylatedisocitrate dehydrogenase wild-typeBayesianadaptive randomization
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.