GlioblastomaPhase 2/3GBM AGILENCT03970447
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
A Phase 2/3 study testing Temozolomide, Lomustine and Regorafenib in people with Glioblastoma, run by Global Coalition for Adaptive Research at 63 sites in 6 countries.
Trial summary
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. All institutions are enrolling Newly Diagnosed participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Temozolomide, Lomustine and Regorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,250 participants
- Where
- 63 sitesin 6 countries
- Study dates
- 30 Jul 2019to Jun 2030
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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, or 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.
Trial locations and contacts
63 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
Sarah Untch contact
63 sites in 6 countries
United States42 sites, 21 recruiting
- Active, not recruiting
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
- Completed
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
- Recruiting
University of Colorado Denver
Aurora, Colorado, 80045
Katherine Harr, 303-724-9693, Katherine.harr@cuanschutz.edu
Denise Damek, MD
- Active, not recruiting
Texas Oncology - Austin
Austin, Texas, 78705
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Thiru Pillay, 205-934-1432, Tpillay@uabmc.edu
Yantong (Lily) Liu, 205-975-2283, yantongliu@uabmc.edu
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Patrick Wen, MD, 617-726-5130, pwen@mgb.org
Patrick Wen, MD
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Amanda Dresser, 617-582-9314, amanda_dresser@dfci.harvard.edu
Kathryn Partridge, 617-582-9314, Kathryn_partridge@dfci.harvard.edu
- Recruiting
Medical University of South Carolina - Hollings Cancer Center
Charleston, South Carolina, 29425
HCC Clinical Trials Office, 843-792-9321, hcc-clinical-trials@musc.edu
Scott Lindhorst, MD
- Recruiting
University of Virginia Health
Charlottesville, Virginia, 22908
CJ Woodburn, 434-243-9900, cjw4v@virginia.edu
David Schiff, MD
- Recruiting
University Hospitals Cleveland Medical Center*
Cleveland, Ohio, 44106
Melissa Brately, 216-983-3021, melissa.brately@UHhospitals.org
Carmen Gray, carmen.gray@UHhospitals.org
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Rachel Hufsey, 216-442-6671, HUFSEYR@ccf.org
Kathy Robinson, 216-444-8923, robinsk2@ccf.org
- Active, not recruiting
Ohio State University Cancer Center
Columbus, Ohio, 43210
- Active, not recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Completed
Henry Ford Health System
Detroit, Michigan, 48202
- Active, not recruiting
Duke University Medical Center
Durham, North Carolina, 27710
- Recruiting
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030
Evguenia Gachimova, RN, (832)266-3519, EGachimova@mdanderson.org
Shiao-Pei Weathers, MD
- Completed
University of Mississippi Medical Center
Jackson, Mississippi, 39213
- Completed
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224
- Recruiting
University of California, San Diego
La Jolla, California, 92093
Sheila Medina, (858) 246-1093, s4medina@health.ucsd.edu
Neuro-Onc_CRC@health.ucsd.edu
- Recruiting
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Shannon Cyhan, GroupCCTOClinicalResearchTeamNeuroOncology@cshs.org
Jethro Hu, MD
- Active, not recruiting
University of California, Los Angeles
Los Angeles, California, 90095
- Recruiting
Sylvester Comprehensive Cancer Center*
Miami, Florida, 33136
Leonela Wright, 305-243-0864, lxw612@med.miami.edu
Macarena I De La Fuente, MD
- Active, not recruiting
Froedtert Hospital/Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Allina Health Systems/Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407
612-863-3452, neurooncologyresearch@allina.com
Andrea Wasilewski, MD
- Recruiting
Yale Cancer Center / Smilow Cancer Hospital*
New Haven, Connecticut, 06511
Amy L. Rodrigues, 203-785-5702, Amy.rodrigues@yale.edu
Nicholas Blondin, MD
- Completed
LSU Health Sciences Center - New Orleans
New Orleans, Louisiana, 70112
- Active, not recruiting
Perlmutter Cancer Center, NYU Langone Health
New York, New York, 10016
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Disha Jain, 929-638-2764, disha.jain@mssm.edu
Lyndon Kim, MD
- Recruiting
Columbia University Medical Center
New York, New York, 10032
Andrew Lassman, MD, 212-342-0571, cancerclinicaltrials@cumc.columbia.edu
Andrew Lassman, MD
- Recruiting
Memorial Sloan Kettering Cancer Center*
New York, New York, 10065
Kerina Yang, 901-883-0840, yangk3@mskcc.org
Nancy Keith, 646-300-0216, KeithN@mskcc.org
- Recruiting
St. Joseph Hospital
Orange, California, 92868
Andrea Torres, 714-734-6220, andrea.torres@providence.org
Lars Anker, MD
- Active, not recruiting
University of Pennsylvania - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
- Completed
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
- Recruiting
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Theo Estep, 878-261-6727, esteptj2@upmc.edu
Brynne Fedor, 878-261-6409, warecolantuoniba3@upmc.edu
- Completed
Mayo Clinic Cancer Center - Rochester
Rochester, Minnesota, 55905
- Recruiting
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Rachel Kingsford, 801-505-0115, rachel.kingsford@hci.utah.edu
Yuri Kida, 801-646-4397, yuri.kida@hci.utah.edu
- Active, not recruiting
University of California, San Francisco
San Francisco, California, 94143
- Active, not recruiting
University of Washington Medical Center
Seattle, Washington, 98101
- Completed
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
- Completed
Stanford Cancer Center
Stanford, California, 94305
- Active, not recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
- Recruiting
Comprehensive Cancer Center of Wake Forest*
Winston-Salem, North Carolina, 272157
Monique Mercado, 336-716-9123, monique.mercado@advocatehealth.org
Glenn Lesser, MD
Australia6 sites, 6 recruiting
- Recruiting
Flinders Medical Centre
Bedford Park, South Australia, 5042
Monique Swan, (08) 8404 2702, Health.FMCCancerResearchNurse@sa.gov.au
Ganessan Kichenadasse, MD
- Recruiting
Austin Health
Heidelberg, Victoria, 3084
Samantha Chakar, (03) 9496 3088, samantha.chakar@austin.org.au
Anne-Marie Woods, 61 9496 3352, anne-marie.woods@austin.org.au
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Allison Hyde, +61 7 36471153, allison.hyde@health.qld.gov.au
Zarnie Lwin, MD
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria
Lucy Willis, +61 3 8559 5000 ext. 1110289, Lucy.Willis@petermac.org
Iris Huang, +61 3 8559 5000 ext. 1110502, Iris.Huang@petermac.org
- Recruiting
Northern Sydney Cancer Centre/Royal North Shore Hospital
St Leonards, New South Wales, 2065
Daisy Yu, (02) 9463 1217, wenqiong.yu@health.nsw.gov.au
Helen Wheeler, MD
- Recruiting
Calvary Mater Newcastle
Waratah, New South Wales, 2298
Kerrie Cornall, +61 (0)2 40143282, Kerrie.Cornall@health.nsw.gov.au
Faisal Hayat, MD
Germany6 sites, 5 recruiting
- Active, not recruiting
Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
Cologne, 50937
- Recruiting
Dr. Senckenbergisches Institut für Neuroonkologie
Frankfurt, 60528
Michael Ronellenfitsch, MD,PhD, +49(0)69 6301 87711, m.ronellenfitsch@med.uni-frankfurt.de
Michael Ronellenfitsch, MD, PhD
- Recruiting
Universitätsklinik Heidelberg
Heidelberg, 69120
Antje Wick, MD, +49 (0) 6221-56 ext. 7075, antje.wick@med.uni-heidelberg.de
Antje Wick, MD
- Recruiting
Universitaetsklinikum Heidelberg - Neurologische Klinik
Mannheim, 68167
Yvonne Neu, +49 621 383-6801, yvonne.neu@umm.de
Michael Platten, MD
- Recruiting
Universitätsklinikum Regensburg
Regensburg, 93053
Peter Hau, MD, +49 (0)941 941-8083, Peter.Hau@ukr.de
Peter Hau, MD
- Recruiting
Universitätsklinikum Tübingen
Tübingen, 72076
Ghazaleh Tabatabai, +49 (0)707 12983269, Ghazaleh.Tabatabai@med.uni-tuebingen.de
Ghazaleh Tabatabai, MD
Canada4 sites, 3 recruiting
- Recruiting
Montreal Neurological Institute and Hospital, McGill University
Montreal, Quebec, H3A 2B4
Gabriele Riva, 514-398-6907, gabriele.riva@mcgill.ca
Emilie Tsiolis, 514-396-1697, emilie.tsiolis@mcgill.ca
- Active, not recruiting
Université de Sherbrooke
Sherbrooke, Quebec, J1H 5H3
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Delareese Mackenzie, 416-480-5000 ext. 7362, delareese.mackenzie@sunnybrook.ca
Shirin Shamsaasef, 416-480-5000 ext. 685841, Shirin.shamsaasef@sunnybrook.ca
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
On Yee Jones, RN, 416-946-4501 ext. 4603, onyee.jones@uhn.ca
Tenzin Yangdol, 416-946-4501 ext. 4624, Tenzin.Yangdol@uhn.ca
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
Bron, 69677
Cecile Novello, 00 33 4 27 85 52 69, cecile.novello01@chu-lyon.fr
Francois Ducray, MD
- Recruiting
Hopital de la Timone
Marseille, 13005
Didier Autran, +334 91 3848 34, didier.autran@ap-hm.fr
Emelie Tabouret, MD
- Recruiting
Hopital Piti-Salpetriere
Paris, 75013
Mehdi Touat, MD, +33 (0)1 42 16 03 81, mehdi.touat@ahph.fr
Mehdi Touat, MD
Switzerland2 sites, 2 recruiting
- Recruiting
Centre Hospitalier Universitaire Vaudois Lausanne
Lausanne, Canton of Vaud, 1011
Andreas Hottinger, MD, +41 79 556 97 74, Andreas.Hottinger@chuv.ch
Andreas Hottinger, MD
- Recruiting
University Hospital Zurich
Zurich
+41 44 255 55 11, neurologie@usz.ch
Michael Weller, MD
About this study
Official title: 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
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.
All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (*).
Read the detailed description
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. Its goals are to identify effective therapies for glioblastoma and match effective therapies with patient subtypes. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to Arms based on their performance. The primary endpoint is overall survival (OS).
GBM AGILE is designed to efficiently evaluate therapies. The trial will be conducted under a single Master Investigational New Drug Application/Clinical Trial Application and Master Protocol, allowing multiple drugs and drug combinations from different pharmaceutical companies to be evaluated simultaneously. The plan is to add experimental therapies as new information about promising new drugs are identified and remove therapies as they complete their evaluation.
- Conditions
- Glioblastoma
- Being tested
- Temozolomide, Lomustine, Regorafenib, Radiation, Paxalisib
- Keywords
- Glioblastoma, Newly diagnosed, recurrent, O6-methylguanine-DNA-methyltransferase (MGMT) methylated, MGMT unmethylated, isocitrate dehydrogenase (IDH) wild-type, Bayesian, adaptive randomization, Master Protocol, Platform Trial, Phase 2, Phase 3
- Medical subject headings
- Glioblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar, Temodal, Temcad
Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg
LomustineDrug
Also called CCNU, CeeNU, Gleostine
Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg
RegorafenibDrug
Also called Stivarga, BAY 73-4506
Dosage Form: Tablet for oral administration Strength: 40 mg Standard Regimen: 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)
RadiationRadiation
60 Gy
PaxalisibDrug
Also called GDC-0084
Dosage Form: Tablet for oral administration Strength: 15 mg Standard Regimen: 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles
VAL-083Drug
Also called Dianhydrogalactitol
Dosage Form: Infusion for intravenous administration Strength: 40 mg per vial Standard Regimen: 30 mg/m2 on Day 1, 2 and 3 of 21-day cycle. The drug is available in powder form. It is reconstituted with 5 mL of 0.9% Sodium Chloride for Injection, USP. This will produce a solution of 40 mg VAL-083 in 5 mL. The required volume of reconstituted VAL-083 for the patient is then calculated at the rate of 30 mg/m2. The corresponding volume is further diluted into 250 mL of 0.9% Sodium Chloride for Injection, USP, prior to intravenous administration.
VT1021Drug
Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).
Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
TroriluzoleDrug
Also called BHV-4157
Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
ADI-PEG 20Biological
Also called Pegargiminase
Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week
AZD1390Drug
Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
TinostamustineDrug
Also called EDO-S101
Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Active comparator | Newly Diagnosed GBM: Radiation therapy (XRT) 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation, and the start of the first cycle of Maintenance Therapy 2-6 weeks after the last day of radiotherapy. The start of all subsequent maintenance therapy cycles (2-12) every 4 weeks + 7 days after the first daily dose of temozolomide of the preceding cycle. Total number of cycles should comply with institutional or country standards. During maintenance therapy, the first cycle of temozolomide will be at 150 mg/m2 for Days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for Days 1-5 of a 28-day cycle.
Recurrent GBM: Lomustine started at 110 mg/m2/day on Day 1 of a 42-day cycle as per local standards. Treatment will continue for up to 6 total cycles. Receives: Drug: Temozolomide; Drug: Lomustine; Radiation: Radiation |
| Regorafenib Treatment Arm- Enrollment concluded | Experimental | Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).
Recurrent GBM: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). Receives: Drug: Regorafenib |
| Paxalisib Treatment Arm- Enrollment concluded | Experimental | Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles.
Recurrent GBM: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 21 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 21 days for all subsequent cycles. Receives: Drug: Paxalisib |
| VAL-083 Treatment Arm- Enrollment concluded | Experimental | Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.
Recurrent GBM: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle. Receives: Drug: VAL-083 |
| VT1021 Treatment Arm - Dose Finding Phase | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. Treatment as outlined in section "Experimental: VT1021 Treatment Arm" with the first 6 patients receiving VT1021 at 12 mg/kg twice weekly in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities reported, the dose will be de-escalated to 9 mg/kg two times a week. 6 patients will then be receiving 9 mg/kg two times a week and observed for DLTs for 4 weeks.
Recurrent GBM: Dose Finding Phase is not applicable for patients with Recurrent GBM in the VT1021 treatment arm. Receives: Drug: VT1021 |
| VT1021 Treatment Arm - Enhanced Safety Management (ESM) | Experimental | Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM) Newly diagnosed MGMT Methylated and Unmethylated GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. PK and PD assessments are done for patients as a part of ESM. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Recurrent GBM: ESM is not applicable for patients with Recurrent GBM in the VT1021 treatment arm. Receives: Drug: VT1021 |
| VT1021 Treatment Arm | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: As confirmed through the dose finding phase) twice weekly during radiation therapy. Rest period: 2-6 weeks from last day of radiation. VT1021 dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with VT1021. After 6 cycles, VT1021 only.
Recurrent GBM: VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: 12mg/kg) twice weekly. Receives: Drug: VT1021 |
| Troriluzole Treatment Arm - Dose Finding Phase | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. The first 6 patients will receive troriluzole at 100 mg BID for the first two weeks followed by 200 mg BID for the next two weeks in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 100 mg in the morning and followed by 200 mg in the evening. 6 patients will receive this dose and observed for 4 weeks. If there are two DLTs reported, then this dose will be de-escalated to 100 mg BID. 6 patients will then be receiving this dose and observed for DLTs for 4 weeks.
Recurrent GBM: Rolling 6 design. The first 6 patients receiving troriluzole 100 mg twice a day (BID) for the first two weeks followed by 200 mg BID for the next two weeks in combination with lomustine. The dose de-escalation is similar to that of newly diagnosed patients during the rolling 6 design. Receives: Drug: Troriluzole |
| Troriluzole Treatment Arm - Enhanced Safety Management (ESM) | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM and Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data. Receives: Drug: Troriluzole |
| Troriluzole Treatment Arm | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. Rest period: 2-6 weeks from last day of radiation. Troriluzole dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with troriluzole. After 6 cycles, troriluzole only.
Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. After 6 cycles, troriluzole only. Receives: Drug: Troriluzole |
| ADI-PEG 20 Treatment Arm - Dose Finding Phase | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: Dose Finding Phase is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.
Recurrent GBM: Rolling 6 design. The first 6 patients will receive ADI-PEG 20 at 36 mg/m2 once a week in combination with lomustine 100 mg/m2 orally on day 1 of a 42-day cycle. 6 patients will receive this dose and be observed for 4 weeks. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 18 mg/m2 once a week. 6 patients will receive this dose and be observed for 4 weeks. Receives: Biological: ADI-PEG 20 |
| ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM) | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: ESM is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.
Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data. Receives: Biological: ADI-PEG 20 |
| ADI-PEG 20 Treatment Arm | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy over 6 weeks. Temozolomide (75 mg/m2 orally daily and ADI-PEG 20 (Dosage Form: Solution for intramuscular injection; Strength: 11.5 ± 1.0 mg/ml; Dose: 36 mg/m2) once a week. Rest period: 2-6 weeks from last day of radiation. ADI-PEG 20 dosing will continue during rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Subsequent cycles will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with ADI-PEG 20. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.
Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with ADI-PEG 20 (Dosage Form: Solution for IM injection; Strength: 11.5 ± 1.0 mg/ml; Dose: As confirmed by dose finding phase, once a week. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment. Receives: Biological: ADI-PEG 20 |
| AZD1390 Treatment Arm | Experimental | Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks in combination with AZD1390 given on days of radiation followed by 14 days with daily AZD1390. Rest Period 2-4 weeks from the last day of AZD1390. The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle, if there is no toxicity. Temozolomide will be administered for up to 6 cycles in the maintenance phase. Receives: Drug: AZD1390 |
| Tinostamustine - Dose finding phase | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: Tinostamustine Dosage Form: Infusion for intravenous administration; Rolling 6 design. Treatment as outlined in "Investigational: Tinostamustine Treatment Arm" with the first 6 patients receiving Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations. If there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).
Recurrent GBM: Rolling 6 design. Tinostamustine Dosage Form: Infusion for intravenous administration; Strength: Starting dose 80 mg/m2 on Day 1 of 21-day cycle for up to 12 cycles. The first 6 patients will receive Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations if there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2). Receives: Drug: Tinostamustine |
| Tinostamustine - Enhanced Safety Management | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: Treatment as outlined in "Investigational: Tinostamustine Treatment Arm". Dose as determined by the dose finding phase.
Recurrent GBM: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase on Day 1 of 21-day cycle for up to 12 cycles. Receives: Drug: Tinostamustine |
| Investigation arm: Tinostamustine | Experimental | Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT total of 60 Gy (2 Gy/fraction) over 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation. Tinostamustine treatment period: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase) on Day 1 of 21-day cycle for up to 12 cycles. Receives: Drug: Tinostamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall survival is defined from the time of randomization to death from any cause. Patients still alive at the time of an analysis will be considered censored at their date of last contact.
Measured: From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Secondary outcomes (3)
Progression-free survival (PFS)
Progression-free survival is defined as the time from randomization to clinically determined progression or death from any cause. All participants will be included in the analysis of PFS.
Measured: From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Tumor Response
Tumor response is categorized by Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Response captured from initiation of study treatment until disease progression.
Measured: From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Duration of Response (CR + PR)
Duration of response (CR+PR) is defined as time from date of response to date of clinically determined disease progression or death from any cause.
Measured: From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study start30 Jul 2019
- Primary completionJun 2028 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- GBM AGILE is a multi-arm, platform trial. The evaluation of each therapy in GBM AGILE may proceed in 2 possible stages. Stage 1 is an adaptively randomized Screening stage for evaluating the therapy within patient signatures compared against a common control. A therapy in Stage 1 will stop accruing patients if it reaches its maximal sample size, drops for limited efficacy, or evinces inadequate safety. If a therapy reaches an efficacy threshold for continuation from Stage 1, it will move into Stage 2 within one of the prospectively defined signatures. The maximum sample size in Stage 1 is 200 patients. For a therapy moving to Stage 2 there is a fixed randomization, expansion cohort. The maximum sample size in Stage 2 is 50 experimental patients in the continued signature. The primary analysis of a regimen's effect on OS uses all patients in both its stages and all control patients in the trial in the continued signature, suitability adjusted for any possible time trends.
- Masking
- None (open label)
- Enrolment
- 2,250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Global Coalition for Adaptive Research
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Kazia Therapeutics Limited, Kintara Therapeutics, Inc., Biohaven Pharmaceuticals, Inc., Vigeo Therapeutics, Inc., Polaris Group, AstraZeneca, Knoa Pharma
- Responsible party
- Sponsor
- Investigators
- Tim Cloughesy, MD, Principal investigator, GCAR CMO and GBM AGILE Global PI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03970447
- Sponsor's protocol ID
- GCAR-7213
- Acronym
- GBM AGILE
- Status last verified
- Jun 2026
- First submitted
- 23 May 2019
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Global Coalition for Adaptive Research (GCAR) is in the planning stages at this time.
Publications
Wen PY, Berry DA, Buxton MB, Colman H, de Groot J, Lim M, Mellinghoff I, Perry JR, Weller M, Blondin NA, Butt OH, Damek DM, de la Fuente MI, Drappatz J, Dunbar E, Giglio P, Hyddmark EV, Iwamoto F, Jaeckle KA, Kim L, Kling HM, Lee EQ, Mantica M, Mikkelsen T, Nabors B, Newton HB, Olson JJ, Schiff D, Walbert T, Weathers SP, Cloughesy T, Lassman AB; GBM AGILE Regorafenib Study Group. Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial. J Clin Oncol. 2026 Jun 20;44(18):1676-1686. doi: 10.1200/JCO-25-01137. Epub 2026 Apr 14.
PubMed 41980234Chen JJ, Vincent MY, Shepard D, Peereboom D, Mahalingam D, Battiste J, Patel MR, Juric D, Wen PY, Bullock A, Selfridge JE, Pant S, Liu J, Li W, Fyfe S, Wang S, Zota V, Mahoney J, Watnick RS, Cieslewicz M, Watnick J. Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors. Commun Med (Lond). 2024 May 21;4(1):95. doi: 10.1038/s43856-024-00520-z.
PubMed 38773224