A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03970447|
Recruitment Status : Recruiting
First Posted : May 31, 2019
Last Update Posted : August 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: Temozolomide Drug: Lomustine Drug: Regorafenib Radiation: Radiation||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||550 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
GBM AGILE is a multi-arm, platform trial. The evaluation of each therapy in GBM AGILE proceeds in 2 possible stages. A therapy's 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 futility, or evinces inadequate safety. If a therapy reaches an efficacy threshold for graduation from Stage 1, it will move into Stage 2 within one of the prospectively defined signatures. The maximum sample size in Stage 1 is 150 patients.
For a therapy graduating to Stage 2 there is a fixed randomization, expansion cohort. The maximum sample size in Stage 2 is 50 experimental patients in the graduating 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 graduating signature, suitably adjusted for any possible time trends.
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||July 30, 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
Active Comparator: Control Arm
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.
Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg
Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg
Experimental: Regorafenib Treatment Arm
Newly Diagnosed 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).
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)
- 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. ]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.
- 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. ]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.
- 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. ]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.
- 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. ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03970447
|Contact: Patient Informationemail@example.com|
|Contact: Rachel Rosenstein-Sisson||RRosenstein.Sisson@GCAResearch.org|
|United States, Michigan|
|Henry Ford Health System||Recruiting|
|Detroit, Michigan, United States, 48202|
|Contact: Tiffany Pearce 313-575-8046 Tpearce1@hfhs.org|
|Principal Investigator: Tommy Mikkelsen, MD|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Lisa Olmos 212-342-5162 firstname.lastname@example.org|
|Principal Investigator: Andrew Lassman, MD|
|Principal Investigator:||Tim Cloughesy, MD||GCAR CMO and GBM AGILE Global PI|