A Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
Overview
- Phase
- Phase 2
- Intervention
- Re-irradiation (RT)
- Conditions
- Glioblastoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 39
- Locations
- 22
- Primary Endpoint
- Overall survival
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing
- •MGMT hypermethylation in archival tumor biopsy, determined by any CLIAapproved, DNA-based assay
- •Prior maximal feasible surgical resection of biopsy
- •Prior treatment with radiation and temozolomide chemotherapy
- •Pathologic and/or Radiographic evidence of recurrent disease
- •Circumscribed enhancing tumor ≤ 5.0 cm in largest diameter (T1 post contrast)
- •1 prior course of radiation therapy
- •Age ≥ 18 years
- •Karnofsky performance status ≥ 70% or ECOG 0 or 1
- •Adequate bone marrow function
Exclusion Criteria
- •Infratentorial location of the recurrence
- •IDH mutated glioblastoma
- •More than one prior tumor recurrence after standard first-line therapy
- •Prior radiation to the brain within ≤ 4 months
- •Circumscribed enhancing tumor \>5.0 cm in largest diameter (T1 post contrast)
- •Pulmonary embolus or deep vein thrombosis within preceding 2 months
- •Grade 2 or greater congestive heart failure
- •Unstable angina, myocardial infarction within past 12 months
- •Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
- •Nonhealing wound, ulcer or bone fracture
Arms & Interventions
Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Intervention: Re-irradiation (RT)
Recurrent Glioblastoma, No Surgery
One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Intervention: Re-irradiation (RT)
Recurrent Glioblastoma, No Surgery
One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Intervention: Bevacizumab
Recurrent Glioblastoma, No Surgery
One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Intervention: Nivolumab
Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Intervention: Bevacizumab
Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Intervention: Nivolumab
Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Intervention: Re-resection
Outcomes
Primary Outcomes
Overall survival
Time Frame: 2 years
in participants with recurrent glioblastoma (first recurrence)treated with re-irradiation with concurrent nivolumab (as well as bevacizumab if the investigator feels that the patient benefits from the addition) followed by adjuvant nivolumab in two parallel cohorts.
Secondary Outcomes
- 6 month progression-free survival(6 months)
- Median progression-free survival(2 years)
- Objective response rate(2 years)