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). (PIRG)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Silesia Katowice Poland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

24 Aug 2022 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2024-517535-52-00

EudraCT number

2020-006143-26

ClinicalTrials.gov

NCT05235737

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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).

Conditions and MedDRA coding

Glioblastoma Multiforme

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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):a) Hemoglobin ≥ 9g/dL , b) Absolute Neutrophils Count (ANC) ≥1.5×10^9/L, c) White Blood Cells (WBC) count ≥3×10^9/L, d) Platelets (PTL) ≥ 100×10^9/L, e) AST/ALT ≤2.5×ULN, f) Serum creatinine (S-Cr) ≤ ULN, g) Glomerular Filtration Rate (GFR) ≥50mL/min, h) Albumin ≥ LLN , i) Bilirubin ≤ 1.5 ULN (except patients with documented Gilbert’s Syndrome, who must present adequate level of direct bilirubin),j) 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 23

1. Any active concomitant malignancy, except: a. Locally treated basal or squamous cell carcinoma b. Cervical carcinoma in situ c. Breast cancer in situ d. Bladder cancer in situ e. Low grade prostate cancer (under observation with PSA level in normal range)
2. Any previous systemic cancer treatment, including, but not limited to: a. Radiotherapy b. Brachytherapy for brain tumor c. Chemotherapy d. Carmustine wafer treatment (Gliadel®) e. 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 less or equal to 12mg of dexamethasone equivalent; the dose of dexamethasone should be kept as low as possible throughout the whole duration of this trial)
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety and tolerability – incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) related and unrelated with Pembrolizumab
2. Patient-Reported Outcomes to evaluate health status and Quality of Life (QoL) instruments for patients with GBM:  Eastern Cooperative Oncology Group (ECOG) status - Karnofsky Performance Status (KPS), - EORTC: QLQ-BN20 (brain), and QLQ-C30 (general cancer questionnaire).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Silesia Katowice Poland

Sponsor organisation

Medical University Of Silesia Katowice Poland

Address

Ul. Ksiecia Jozefa Poniatowskiego 15

City

Katowice

Postcode

40-055

Country

Poland

Scientific contact point

Organisation

Medical University Of Silesia Katowice Poland

Contact name

Clinical trial information desk

Public contact point

Organisation

Medical University Of Silesia Katowice Poland

Contact name

Clinical trial information desk

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications