UCSF BTC Clinical Trials

Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma

 

Summary

The purpose of this study is to evaluate the safety and efficacy of the combination of Avelumab and re-irradiation therapy, for patients with IDH mutant gliomas that have transformed to glioblastoma after chemotherapy.

Avelumab is an antibody that specifically targets and blocks interactions between proteins called PD-L1 and PD-1. PD-1 is a protein that normally protects the body from attacking itself. It does so by detecting PD-L1, which acts as a signal made by various cells across the body. Some cancer cells take advantage of this protection mechanism making the protective signal themselves. Blocking PD-L1 with Avelumab disrupts this protection mechanism, allowing the immune system activate T cells and recognize the tumors as cells to be attacked.

All eligible participants will receive the following treatment:

  • Experimental Group: Avelumab + hypofractionated radiation therapy

 

Inclusion Criteria
  1. Male or female subjects aged ≥18 years.
  2. Documentation of IDH1 or IDH2 mutation in any tumor specimen.
  3. A diagnosis of WHO grade II or III glioma prior to treatment with temozolomide or PCV chemotherapy.
  4. Histopathological evidence of glioblastoma (WHO grade IV) on a progressive tumor specimen after treatment with temozolomide or PCV chemotherapy.
  5. Any progressive glioma with IDH1 or IDH2 mutation, regardless of WHO grade or histopathological diagnosis, with ≥20 somatic mutations per Mb by whole-exome sequencing; (2) mutation in a mismatch repair gene or other genes known to be associated with hypermutator phenotypes or microsatellite instability; or (3) microsatellite instability
  6. Treatment with temozolomide or PCV [procarbazine, lomustine (CCNU), vincristine] chemotherapy prior to histopathologic transformation to glioblastoma or prior to identification of one of the genetic alterations specified above.
  7. Unequivocal radiographic evidence of tumor progression by contrast-enhanced MRI scan (or CT scan if MRI is contraindicated).
  8. Karnofsky performance status of ≥60.
  9. Interval of at least 6 months from the completion of any prior radiotherapy and registration.

For the full list of criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. Investigational drug use within 28 days of the first dose of Avelumab.
  2. Planned participation in another study of an investigational agent or investigational device or use of a therapeutic device intended for therapy of glioma.
  3. Prior therapy with an agent that blocks the PD-1/PD-L1 pathway.
  4. Primary brainstem or spinal cord tumor.
  5. Prior re-irradiation or stereotactic radiosurgery for recurrent disease at the same tumor location
  6. Patients with evidence of significant intracranial mass effect that requires >4 mg of dexamethasone or bioequivalent per day for 5 consecutive days for management of symptoms at any time within 14 days of registration.
  7. Known immunosuppressive disease, active autoimmune disease requiring chronic immunosuppressive therapy, prior organ transplant, including allogeneic stem cell transplantation. The following are not exclusions: Diabetes type I, Vitiligo, hypo- or hyperthyroid, or psoriasis that does not require systemic immunosuppressive treatment are eligible 
  8. Active infection requiring systemic therapy, including known infection with human immunodeficiency virus (HIV), or known active infection with hepatitis B or hepatitis C virus
  9. Patients with another active cancer [excluding basal cell carcinoma, cervical carcinoma in situ or melanoma in situ]. Prior history of other cancer is allowed, as long as there was no active disease within the prior 2 years.
  10. Unstable or severe intercurrent medical or psychiatric conditions or uncontrolled infection.
  11. Pregnant or breastfeeding (negative pregnancy test required), or unable to maintain use of contraception while on study and for 60 days after the last dose of Avelumab.
  12. Known alcohol or drug abuse
  13. All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment.
  14. Any psychiatric condition that would prohibit the understanding or rendering of informed consent

For the full list of criteria, please visit clinicaltrials.gov.

Investigator(s)

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