Clinical Trials /

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

NCT03970447

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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

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

  • Glioblastoma

Interventions

DrugSynonymsArms
TemozolomideTemodar, Temodal, TemcadControl Arm
LomustineCCNU, CeeNU, GleostineControl Arm
RegorafenibStivarga, BAY 73-4506Regorafenib 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

NameTypeDescriptionInterventions
Control ArmActive ComparatorNewly 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.
  • Temozolomide
  • Lomustine
Regorafenib Treatment ArmExperimentalNewly 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).
  • Regorafenib

Eligibility Criteria

        Newly Diagnosed Inclusion Criteria:

          -  Age ≥ 18 years.

          -  Histologically confirmed Grade IV GBM/gliosarcoma established following either a
             surgical resection or biopsy.

          -  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 GBM/gliosarcoma (WHO criteria; non-IDH R132H mutant) at first
             or second recurrence after initial standard, control or experimental therapy that
             includes at a minimum Radiation Therapy (RT).

          -  Evidence of recurrent disease (RD) demonstrated by disease progression using slightly
             modified Response Assessment in Neuro-Oncology (RANO) criteria.

          -  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:

          -  Any prior treatment for glioma including: prior prolifeprospan 20 with carmustine
             wafer; prior intracerebral agent; prior radiation treatment for GBM or lower-grade
             glioma; 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 3 years, with a disease-free interval of
             < 3 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.)

          -  Any prior treatment with bevacizumab or other VEG)- 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. Participant 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