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.
Title
- Brief Title: A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
- 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
Clinical Trial IDs
- ORG STUDY ID:
GCAR-7213
- NCT ID:
NCT03970447
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Temozolomide | Temodar, Temodal, Temcad | Control Arm |
Lomustine | CCNU, CeeNU, Gleostine | Control Arm |
Regorafenib | Stivarga, BAY 73-4506 | Regorafenib Treatment Arm |
Paxalisib | GDC-0084 | Paxalisib Treatment Arm |
VAL-083 | Dianhydrogalactitol | VAL-083 Treatment Arm |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
Regorafenib Treatment Arm | 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). | |
Paxalisib Treatment Arm | 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. | |
VAL-083 Treatment Arm | 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. | |
Eligibility 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 > 450 msec if male and QTc > 470 msec if female.
- 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 > 450 msec if male and QTc > 470 msec if female.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Survival (OS) |
Time Frame: | 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. |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Progression-free survival (PFS) |
Time Frame: | 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. |
Safety Issue: | |
Description: | 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. |
Measure: | Tumor Response |
Time Frame: | From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first. |
Safety Issue: | |
Description: | 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. |
Measure: | Duration of Response (CR + PR) |
Time Frame: | 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. |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Global Coalition for Adaptive Research |
Trial 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
Last Updated
August 20, 2021