A Single Center, Open-Label, Randomized Study to Evaluate the Safety and Efficacy of Neoadjuvant and Adjuvant Pembrolizumab on Top of Standard Chemo-Radiotherapy (Stupp Protocol) in Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme (GBM).

Trial ID: NCT05235737

Interventional - Phase 4 - Unknown status

To evaluate the short-term and longer-term safety, tolerability, and effectiveness of neoadjuvant and adjuvant Pembrolizumab on top of standard therapy (Stupp protocol) in patients with Glioblastoma Multiforme (GBM). Randomized comparison of safety, tolerability, and clinical efficacy of (1) neoadjuvant and adjuvant Pembrolizumab (on top of Stupp protocol, n=12 patients), (2) neoadjuvant Pembrolizumab (on top of Stupp protocol, n=12 patients), and (3) standard of care (Stupp protocol only, n=12 patients). Immuno-PET examination will be performed before and after surgery in all patients.

Conditions

• Newly Diagnosed Glioblastoma

Interventions

• Pembrolizumab
• Pembrolizumab

Eligibility

Inclusion criteria

• 1. Signed Informed Consent Form
• 2. Age ≥ 18 years
• 3. Age ≤70 years
• 4. Able to comply with the study protocol in the investigator's judgment
• 5. Clinically and radiologically (contrast CT, full profile MRI - T1-weighted with or without contrast, T2-weighted, FLAIR, DWI, PWI, MR-spectroscopy) confirmed diagnosis of GBM, localized outside eloquent brain areas
• 6. Resectable tumor
• 7. Fully physically active ≥80 points in Karnofsky performance scale
• 8. Life expectancy of at least 3 months
• 9. Adequate organ function (confirmed within 1 weeks before enrollment):
• 1. Hemoglobin ≥ 9g/dL
• 2. Absolute Neutrophils Count (ANC) ≥1.5×109/L
• 3. White Blood Cells (WBC) count ≥3×109/L
• 4. Platelets (PTL) ≥ 100×109/L
• 5. AST/ALT ≤2.5×ULN
• 6. Serum creatinine (S-Cr) ≤ ULN
• 7. Glomerular Filtration Rate (GFR) ≥50mL/min
• 8. Albumin ≥ LLN
• 9. Bilirubin ≤ 1.5 ULN (except patients with documented Gilbert's Syndrome, who must present adequate level of direct bilirubin)
• 10. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN. (Elevation of INR and aPTT due to administration of anticoagulation drugs is not a contraindication for the enrollment. However, it must return to normal range prior to surgery).
• 10. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use double barrier contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last immuno-PET imaging.
• 11. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use double barrier contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last immuno-PET imaging.

Exclusion criteria

• Patients who meet any of the following criteria will be excluded from study entry:
• 1. Any active concomitant malignancy, except:
• 1. Locally treated basal or squamous cell carcinoma
• 2. Cervical carcinoma in situ
• 3. Breast cancer in situ
• 4. Bladder cancer in situ
• 5. Low grade prostate cancer (under observation with PSA level in normal range)
• 2. Any previous systemic cancer treatment, including, but not limited to:
• 1. Radiotherapy
• 2. Brachytherapy for brain tumor
• 3. Chemotherapy
• 4. Carmustine wafer treatment (Gliadel®)
• 5. Any immune checkpoint inhibitor therapy or any anticancer vaccination
• 3. Hypersensitivity or allergy to any substance with similar action mechanism to Pembrolizumab, Atezolizumab, Temozolomide, other monoclonal antibodies or contrast agents
• 4. Any active immunosuppressive systemic therapy (except corticosteroids under 12mg)
• 5. Any active autoimmune disease or systemic therapy for autoimmune disease within 2 years before enrollment
• 6. History of any immunodeficiency
• 7. Active infection
• 8. Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, coronary artery disease, unstable arrhythmias or unstable angina
• 9. Active liver disease, hepatitis, HBV or HCV infection
• 10. History of tuberculosis
• 11. Any mental disorder that may affect patient's participation
• 12. Any drug or psychoactive substance dependence
• 13. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol
• 14. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
• 15. Major surgical procedure within 4 weeks prior to study enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
• 16. Any live vaccination within 30 days before enrollment
• 17. Any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection
• 18. Body mass index (BMI) ≥ 35 kg/m2
• 19. Pregnant or lactating or intending to become pregnant during the study - women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study treatment
• 20. Any condition that the patient's physician determines to be detrimental to the patient participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events.
• 21. Inability to understand the local language for use of the patient QoL instruments.
• 22. Tumor other than glioblastoma grade 4 IDH-wildtype, astrocytoma grade 3 or 4 IDH-mutant identified in post-surgery histopathology.
• 23. Presence of 1p19q codeletion.

Sponsor

Medical University of Silesia, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice

Source: ClinicalTrials.gov

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