PHASE2RECRUITING

Comparing 17 approaches for glioblastoma

Official title: A Trial to Evaluate Multiple Regimens in 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

Condition: GlioblastomaSponsor: Global Coalition for Adaptive ResearchTarget enrollment: 2250

Interventions

DRUG

Temozolomide

Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg

DRUG

Lomustine

Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg

DRUG

Regorafenib

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)

RADIATION

Radiation

60 Gy

DRUG

Paxalisib

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

DRUG

VAL-083

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.

DRUG

VT1021

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.

DRUG

Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

BIOLOGICAL

ADI-PEG 20

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

DRUG

AZD1390

Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.

DRUG

Tinostamustine

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.

Canadian Sites (4)

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

RECRUITING

Montreal Neurological Institute and Hospital, McGill University

Montreal, Quebec, Canada

RECRUITING

Université de Sherbrooke

Sherbrooke, Quebec, Canada

ACTIVE_NOT_RECRUITING

See who this study is looking for26 criteria

The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.

Inclusion

+Age ≥ 18 years.
+Age ≥ 18 years.
+Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
+Recurrent Inclusion Criteria:
+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.
+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. 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.
+Availability of tumor tissue representative of GBM from definitive surgery or biopsy.
+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).
+Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Exclusion

−Extensive leptomeningeal disease.
−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.
−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
−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.
−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.
−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.)

5 concepts to explore on this page · up to 1,300 pointsTap any term to learn what it means.

In plain language

Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.

Learning

What this study is

This study is testing a treatment for a condition.

Phase 2/3 — a combined study that runs the middle stage and the large comparison stage together.

What is being given or done in this study: Temozolomide, Lomustine, Regorafenib, Radiation, and 7 more.

From the trial registry

Built from these fields:

designModule.designInfo.primaryPurpose
designModule.phases
armsInterventionsModule.interventions[].name

How the study is run

Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.

This study is open-label: everyone knows which treatment is being given, including you and the study team.

From the trial registry

Built from these fields:

designModule.designInfo.allocation
designModule.designInfo.maskingInfo.masking

Is there a placebo?

This study does not list a placebo group.

One group receives an existing treatment, so the two can be compared.

There are 17 groups in this study.

From the trial registry

Built from this field:

armsInterventionsModule.armGroups[].type

Who the study is looking for

The study lists a minimum age of 18 years, with no upper limit given.

The study is open to people of any sex.

The study does not accept healthy volunteers.

These are the criteria the study lists. Only the trial site can decide whether someone can take part.

From the trial registry

Built from these fields:

eligibilityModule.minimumAge
eligibilityModule.sex
eligibilityModule.healthyVolunteers

How big and how long

The study aims to enrol about 2,250 people.

The study is currently expected to finish around June 2030.

The main measurement is taken over: 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.

From the trial registry

Built from these fields:

designModule.enrollmentInfo.count
statusModule.completionDateStruct.date
outcomesModule.primaryOutcomes[].timeFrame

What the study measures

Overall Survival (OS) — measured over 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.

From the trial registry

Built from these fields:

outcomesModule.primaryOutcomes[].measure
outcomesModule.primaryOutcomes[].timeFrame

Source: NCT03970447 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.

Not medical advice. What do these terms mean?

What is being tested — in plain terms

About TemozolomideDrug

Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg