A Phase II/III Study of Regorafenib, Paxalisib, and VAL-083 versus Standard Therapy for Patients with Newly Diagnosed or Recurrent Glioblastoma (GBM AGILE)

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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 Glioblastoma (GBM)

Purpose

The purpose of this study is to evaluate the effectiveness of treating patients with recurrent and newly diagnosed glioblastoma using new therapies that are thought to be effective for treating brain cancer. The new therapies available as part of this clinical trial include regorafenib, VAL-083, and paxalisib.

Regorafenib is a drug used to treat certain digestive cancers. It may also be active against glioblastoma multiforme (GBM), an aggressive brain tumor. Regorafenib works by blocking an enzyme that cancer cells need to grow. Blocking this enzyme inhibits the development of blood vessels that cancer cells need to grow and spread.

VAL-083 works by targeting DNA (a molecule that contains information needed for cells to develop, live, and reproduce). By targeting the DNA in cancer cells, researchers believe this will help stop cancer cell growth. VAL-083 is thought to be more effective than the FDA-approved drug temozolomide, because it targets DNA differently and may also stop the growth of cancers that are resistant to temozolomide.

Paxalisib is a medication that works by targeting the PI3-kinase (PI3K) pathway, which is critical for the growth of cancer cells. Researchers believe that this pathway is particularly active in glioblastoma, because these tumors often have changes in genes the belong to this signaling pathway. PI3K inhibitors have already been FDA-approved and are being used for the treatment of other cancers.

Patients in this study will be randomly assigned to receive either:

  • Temozolomide and radiation therapy for patients with newly diagnosed “unmethylated” GBM.
  • Lomustine for recurrent GBM.
  • Regorafenib. Patients in this group with newly diagnosed GBM will receive temozolomide and radiation therapy before starting treatment with regorafenib.
  • VAL-083. Patients in this group with newly diagnosed GBM will receive temozolomide and radiation therapy before starting treatment with VAL-083. Patients with recurrent glioblastoma will not undergo radiation and temozolomide treatment, and will receive only VAL-083.
  • Paxalisib. Patients in this group with newly diagnosed GBM will receive temozolomide and radiation therapy before starting treatment with paxalisib. Patients with recurrent glioblastoma will not undergo radiation and temozolomide treatment, and will receive only paxalisib.

Regorafenib, lomustine, and paxalisib are taken orally (by mouth), and VAL-083 is given intravenously (by vein).

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have newly diagnosed or recurrent GBM.
  • Patients with recurrent GBM may not participate if they had more than two prior regimens of chemotherapy, prior treatment with bevacizumab or another drug that inhibits tumor blood vessel growth, or previous therapy with prolifeprospan 20 with carmustine wafer or a medication delivered directly into the brain.
  • Patients must be able to walk and do routine activities for more than half of their normal waking hours.
  • This study is for patients age 18 and older.

For more information about this study and to inquire about eligibility, please contact Dr. Ingo Mellinghoff at 646-888-2766.

Protocol

19-346

Phase

II/III

Disease Status

Newly Diagnosed & Relapsed/Refractory

Investigator

Co-Investigators