Evaluating Pembrolizumab in Newly Diagnosed Glioblastoma Patients

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).

This study is testing if adding a drug called Pembrolizumab to standard treatment can help people with newly diagnosed glioblastoma feel better and improve their outcomes.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Medical University of Silesia (Academic / other)
• Drugs / interventions: Pembrolizumab, Atezolizumab, Chemotherapy, immunotherapy
• Locations: 1 site (Sosnowiec, Silesian)
• Trial ID: NCT05235737 on ClinicalTrials.gov

What this trial studies

This study assesses the safety, tolerability, and effectiveness of Pembrolizumab when used as both neoadjuvant and adjuvant therapy in patients with newly diagnosed Glioblastoma Multiforme (GBM). Participants will be randomly assigned to one of three treatment arms: receiving Pembrolizumab alongside standard therapy, Pembrolizumab only in the neoadjuvant phase, or standard therapy alone. The study will include up to 36 patients and will utilize Immuno-PET imaging to evaluate immune response before and after surgery. The aim is to determine the potential benefits of adding Pembrolizumab to the established treatment regimen for GBM.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a confirmed diagnosis of resectable Glioblastoma localized outside eloquent brain areas.

Not a fit: Patients with non-resectable tumors or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with Glioblastoma.

How similar studies have performed: Previous studies have shown promise in using Pembrolizumab for various cancers, but this specific application in GBM is relatively novel.

Eligibility 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.

Where this trial is running

Sosnowiec, Silesian

• Wojciech Kaspera — Sosnowiec, Silesian, Poland (Recruiting)

Study contacts

• Study coordinator: Wojciech Kaspera, Md, Phd

Conditions Newly Diagnosed Glioblastoma; Glioblastoma, Pembrolizumab, Immunotherapy, PD-1, PD-L1