Glioblastoma Multiforme
Conditions
Keywords
Central Nervous System Tumor, neurosurgery, Brain tumor, spinal cord tumor, surgical resection, glioma, glioblastoma, neuropathology, maximal safe resection, CNS
Brief summary
The purpose of this study is to assess the safety/tolerability/feasibility of pembrolizumab and radiation therapy before surgical resection in patients with recurrent glioblastoma as defined by treatment-related AEs and the number of patients who do not necessitate a delay in surgical resection, and to assess overall survival. The secondary objectives are to assess progression free survival, and to assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment
Interventions
DRUGPembrolizumab
Pembrolizumab 400mg administered intravenously on Day 1, and then beginning 6 weeks post-surgery, subjects will receive 400 mg pembrolizumab every 6 weeks
RADIATIONStereotactic Radiation Therapy
Standard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7
PROCEDURESurgical Resection
Standard of care surgical resection of tumor on Day 10-28
Sponsors
Merck Sharp & Dohme LLC
National Cancer Institute (NCI)
Chirag G. Patil
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Confirmed histologic diagnosis of WHO Grade IV, Glioblastoma Multiforme * GBM recurrence or progression with planned standard of care surgical resection and repeat radiation * Tumor size less than 6 cm * ECOG performance status of 0-1 * Adequate laboratory values
Exclusion criteria
* Contraindication to additional radiation * Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor * Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone) or any other form of immunosuppressive therapy * Severe hypersensitivity to pembrolizumab Complete inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events. | From start of study treatment until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years. | Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events as assessed per CTCAE, Version 5.0. |
| Overall survival | From start of study treatment until death, loss to follow-up, or withdrawal of consent. Assessed up to 2 years. | From start of study treatment until death, loss to follow-up, or withdrawal of consent. Subjects who are lost to survival follow-up will not be replaced, and public records may be accessed to assess Overall Survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | From start of study treatment until until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years. | From start of study treatment until confirmation of disease progression (per iRANO Criteria), intolerable toxicities, withdrawal of consent, or up to 2 years or 18 cycles of pembrolizumab, whichever comes first. |
| Immune action | At baseline, prior to stereotactic radiation therapy, and prior to surgery. | To assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment. Blood draws for research purposes performed after obtaining consent but prior to neoadjuvant pembrolizumab administration, and at the time of initiation of SRT and at the time of surgery |
Countries
United States
Contacts
Primary ContactClinical Trial Recruitment Navigator
Outcome results
None listed