Glioblastoma Adaptive, Global, Innovative Learning Environment (GBM AGILE)

ENROLLING
Protocol # :
19-429
Conditions
Glioblastoma
Phase
II/III
Disease Sites
Brain and Nervous System
Principal Investigator
Wen, Patrick, Yung
Site Investigator
Gerstner, Elizabeth, R.
Gerstner, Elizabeth, R.
Miller, Julie, JoAnn
Site Research Nurses
Aste, Marie, Francesca
Chau, Johny, E.
Hibyan, Lauren, M.
Kuberski, Heather, D.
Markt, Denise, A.
Pedro, Christine

Trial 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.

Eligibility Requirements

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.

19-429