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Alkylating agents

Multiple Therapies for Glioblastoma (GBM AGILE Trial)

Phase 2 & 3

Recruiting

Led By Tim Cloughesy, MD

Research Sponsored by Global Coalition for Adaptive Research

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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).

Age ≥ 18 years.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Awards & highlights

GBM AGILE Trial Summary

This trial is designed to test multiple therapies for glioblastoma, a type of brain cancer.

Who is the study for?

This trial is for adults with Grade IV Glioblastoma, confirmed by specific tests. Participants must have a certain level of physical function (Karnofsky performance status ≥ 60% or ≥ 70%). They should have had an MRI recently and available tumor tissue samples. It's not suitable for those who don't meet these criteria.Check my eligibility

What is being tested?

The study is testing multiple drugs like Lomustine, VAL-083, and Temozolomide alongside Radiation and others in patients with new or recurrent Glioblastoma. It's a global trial that adapts as it learns from the results to find the best treatment options.See study design

What are the potential side effects?

Potential side effects may include fatigue, nausea, hair loss due to chemotherapy and radiation, neurological changes from disease progression or treatments, liver issues from targeted therapies, and possible allergic reactions.

GBM AGILE Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain tumor is a Grade IV GBM or gliosarcoma, confirmed by tests, and has recurred after initial treatment including radiation.

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I am 18 years old or older.

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I can provide a sample of my tumor from surgery or biopsy.

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I have recently been diagnosed with my condition.

GBM AGILE Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 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.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~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.

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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. for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Overall Survival (OS)

Secondary outcome measures

Duration of Response (CR + PR)

Progression-free survival (PFS)

Tumor Response

GBM AGILE Trial Design

13Treatment groups

Experimental Treatment

Active Control

Group I: VT1021 Treatment Arm - Enhanced Safety Management (ESM)Experimental Treatment1 Intervention

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.

Group II: VT1021 Treatment Arm - Dose Finding PhaseExperimental Treatment1 Intervention

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.

Group III: VT1021 Treatment ArmExperimental Treatment1 Intervention

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.

Group IV: VAL-083 Treatment ArmExperimental Treatment1 Intervention

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.

Group V: Troriluzole Treatment Arm - Enhanced Safety Management (ESM)Experimental Treatment1 Intervention

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.

Group VI: Troriluzole Treatment Arm - Dose Finding PhaseExperimental Treatment1 Intervention

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.

Group VII: Troriluzole Treatment ArmExperimental Treatment1 Intervention

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.

Group VIII: Regorafenib Treatment ArmExperimental Treatment1 Intervention

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).

Group IX: Paxalisib Treatment ArmExperimental Treatment1 Intervention

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.

Group X: ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)Experimental Treatment1 Intervention

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.

Group XI: ADI-PEG 20 Treatment Arm - Dose Finding PhaseExperimental Treatment1 Intervention

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.

Group XII: ADI-PEG 20 Treatment ArmExperimental Treatment1 Intervention

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.

Group XIII: Control ArmActive Control3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Troriluzole

2019

Completed Phase 3

~890

ADI-PEG 20

2013

Completed Phase 2

~190

Regorafenib

2014

Completed Phase 2

~1580

0 / 4Eligibility criteria met

Find a Location

Who is running the clinical trial?

Global Coalition for Adaptive ResearchLead Sponsor

1 Previous Clinical Trials

20,000 Total Patients Enrolled

BayerIndustry Sponsor

2,240 Previous Clinical Trials

25,331,747 Total Patients Enrolled

5 Trials studying Glioblastoma

114 Patients Enrolled for Glioblastoma

Kintara Therapeutics, Inc.Industry Sponsor

4 Previous Clinical Trials

164 Total Patients Enrolled

2 Trials studying Glioblastoma

149 Patients Enrolled for Glioblastoma

Media Library

Lomustine (Alkylating agents) Clinical Trial Eligibility Overview. Trial Name: NCT03970447 — Phase 2 & 3

Glioblastoma Research Study Groups: Troriluzole Treatment Arm - Dose Finding Phase, Control Arm, Paxalisib Treatment Arm, VAL-083 Treatment Arm, VT1021 Treatment Arm - Dose Finding Phase, VT1021 Treatment Arm - Enhanced Safety Management (ESM), VT1021 Treatment Arm, Troriluzole Treatment Arm - Enhanced Safety Management (ESM), Troriluzole Treatment Arm, ADI-PEG 20 Treatment Arm - Dose Finding Phase, ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM), ADI-PEG 20 Treatment Arm, Regorafenib Treatment Arm

Glioblastoma Clinical Trial 2023: Lomustine Highlights & Side Effects. Trial Name: NCT03970447 — Phase 2 & 3

Lomustine (Alkylating agents) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03970447 — Phase 2 & 3

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Has this specific research been conducted before?

"Since 2002, VAL-083 has undergone extensive research with the first study being completed by Schering-Plough. This initial study had 60 participants and, as a result of its success, VAL-083 received Phase 2 drug approval. Now, 302 trials are being conducted in 1175 cities across 42 countries."

Answered by AI

Are there slots open for more participants in this research project?

"This study is currently recruiting participants, as indicated on clinicaltrials.gov. The trial was first posted on 7/30/2019 and was most recently updated on 10/29/2022."

Answered by AI

Where are the different sites for this trial taking place?

"Some of the many locations where this trial is being conducted are Henry Ford Health System in Detroit, Michigan, Columbia University Medical Center in New york, New York, and Memorial Sloan Kettering Cancer Center in Birmingham, Alabama."

Answered by AI

What are the most common treatments VAL-083 is used for?

"procarbazine is often paired with VAL-083, which is also effective at treating liver carcinoma, brain, and glioblastoma multiforme (gbm)."

Answered by AI

What other studies have used VAL-083 as a treatment?

"The first clinical study for VAL-083 was completed at Memorial Sloan Kettering Cancer Center in 2002. As of now, there are a total of 460 clinical trials that have been completed. Additionally, there are 302 studies that are still ongoing, with a large portion taking place in Detroit, Michigan."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma

2019. "A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03970447.

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