Glioblastoma multiforme MedDRA version: 18.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Clinica Universidad de Navarra/Universidad de Navarra
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study. 3. Patients with GBM that are candidates to primary or salvage resection surgery, according to the following criteria: a. in patients undergoing primary surgery, diagnosis of GBM should be confirmed by previous biopsy or previous partial resection. b. in patients with recurrent GBM, diagnosis of progression will be confirmed either by previous biopsy or by the Revised Assessment in Neuro-Oncology (RANO) criteria, as assessed by the investigator (appendix 1). 4. Patients may have received previous treatments for GBM. There is no limit on previous treatment lines, as long as the other inclusion criteria are met. 5. Patients in whom surgery can be safely delayed for a minimum period of 2 weeks following the administration of the first dose of nivolumab, in the opinion of the investigator. 6. ECOG performance status of 0-1. Patients with ECOG>1 due to neurological symptoms considered to be reversible following surgery, according to investigator´s criteria will be eligible. 7. Life expectancy >12 weeks. 8. Steroids should be ideally discontinued or reduced to a dose 40 ml/min, using the Cokcroft-Gault formula. 10. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. 11. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab 12. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. 13. Patients must be at least 18 years old. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: 1. Presence of extracranial disease. 2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive the planned therapy (including brain surgery), or interfere with the interpretation of study results. 3. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 4. Previous treatment with a PD-1, PDL1 or CTLA-4 targeted therapy 5. Treatment with any anti-cancer drug or radiation therapy within the last 14 days. A shorter interval can be approved by the principal investigator, if deemed appropriate. 6. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents), with the exception of control of cerebral edema, or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 7. Pregnant or breastfeeding patients. 8. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Routine testing is not required. 9. Positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection. 10. History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies. 11. Prisoners or subjects who are involuntarily incarcerated or who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. 12. Subjects unable (due to existent medical condition, e.g, pacemaker or implantable cardioverter defibrillator device) or unwilling to have a head contrast enhanced MRI and/or a CT scan of the brain. 13. Concomitant or prior malignancy that, in the opinion of the investigator contraindicates GBM surgery or can interfere with the results of the study, in the opinion of the investigator. 14. Known drug or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 2.1 Main objective. To assess changes in PD-L1 and CD8 expression induced by neoadjuvant nivolumab in GBM. For that purpose we will compare GBM tissue of patients before and after treatment with neoadjuvant nivolumab.;Primary end point(s): Changes in CD8 and PDL1 expression after one dose of nivolumab;Timepoint(s) of evaluation of this end point: Day 15 of the trial (after one neoadjuvant dose);Secondary Objective: 2.2 Secondary objectives. To determine: - Progression-free survival (PFS) and overall survival (OS) in all patients. - Safety of neoadjuvant nivolumab in patients with GBM. - Tumor and peripheral blood biomarkers with potential predictive of pharmacodynamic effects and clinical activity. - Early tumor response to the neoadjuvant dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (PFS) and overall survival (OS) in all patients. - Safety of neoadjuvant nivolumab in patients with GBM. - Tumor and peripheral blood biomarkers with potential predictive of pharmacodynamic effects and clinical activity. - Early tumor response to the neoadjuvant dose;Timepoint(s) of evaluation of this end point: All throughout the trial | — |
Countries
Spain
Contacts
Public ContactUCEC
Clinica Universidad de Navarra
Outcome results
None listed