Clinical Trial 20110

• Overview

  Study Title:

  GBM Agile: Global Adaptive Trial Master Protocol

  Summary:

  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.

  Objective:

  5.1 Primary Objectives The primary objectives of the study are: 1. To identify experimental therapies that improve OS for GBM patients in the Screening stage (Stage 1), determining if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment. 2. To confirm identified efficacious experimental therapies and associated biomarker signatures in an expansion stage (Stage 2) designed to support a new drug application. 5.2 Secondary Objectives The secondary objectives of the study are: 1. To evaluate PFS by each biomarker/therapeutic combination. 2. To evaluate OS by each biomarker/therapeutic combination. 3. To determine short- and long-term safety signals and QOL measures of an experimental Arm in GBM patients versus standard of care. 5.3 Exploratory Objectives The primary objectives of the study are: 1. To generate general prognostic and predictive biomarker hypotheses. 2. To build and validate a longitudinal endpoint model of OS comprised of early assessments (performance status, disease progression, etc.) that are associated with OS.

• Treatments

  Therapies:

  Chemotherapy (NOS); Radiotherapy; Therapy (NOS)

  Medications:

  ADI-PEG 20 (); BAY 73-4506 (Regorafenib); Lomustine (CeeNU); Paxalisib (); Regorafenib (Stivarga); Temodal (Temozolomide); Temozolomide (); Troriluzole (); VAL-083 (); VT1021 ()

• Inclusion Criteria

  • Newly Diagnosed Inclusion Criteria:
  • 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:
  • 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.

• Exclusion Criteria

  • 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 2 years, with a disease-free interval of >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.

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