Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme

NCT03047473 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CNO-006
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a safety and tolerability study looking at the addition of avelumab, an immune checkpoint inhibitor, to standard therapy of temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. All patients will be receiving active therapy. Patients will begin the avelumab within 3 weeks of finishing their radiotherapy. Avelumab will be given at a dose of 10mg/kg IV every 2 weeks concomitantly with the monthly temozolomide. Avelumab will be continued for a total of 52 weeks.

Conditions

Glioblastoma Multiforme of Brain

Keywords

newly diagnosed

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  The number of patients with an avelumab related adverse event leading to permanent or transient discontinuation of avelumab treatment. Treatment related adverse events of special interest will include those of autoimmune origin (irAE). The adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0

  over the course of the 52 weeks stsudy

Secondary Outcomes (1)

• Safety and Tolerability

  over the course of the 52 weeks study

Study Arms (1)

Newly diagnosed GBM

EXPERIMENTAL

single arm, open label Addition of Avelumab to standard treatment

Biological: avelumab

Interventions

avelumab BIOLOGICAL

add on of avelumab 10mg/kg IV to standard therapy

Newly diagnosed GBM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Age ≥ 18 years.
• Present with newly diagnosed supratentorial Glioblastoma (GBM) with a tissue diagnosis that has been established following either a surgical resection or biopsy. This includes treatment-naïve -(chemotherapy and radiotherapy)- patients with prior diagnosis of a lower grade astrocytoma that has been upgraded to a histologically verified GBM.
• Karnofsky performance score of 70 or higher.
• Patients entering the study must be on a stable dose of up to 12 mg (maximum) of Dexamethasone (or equivalent) daily for symptoms related to cerebral edema. Following the first dose of avelumab, the duration of treatment with the current dose of dexamethasone (maximum 12 mg/day) or equivalent, should be no more than 7 consecutive days. The investigator(s) should make every effort to taper the dexamethasone as soon as symptom improvement allows to the lowest tolerable dose that controls the CNS symptoms.
• Will be or is undergoing or has received the standard therapy of chemo radiation therapy (60Gy in 30 fractions of 2Gy/day with concurrent temozolomide of 75mg/m2 per day PO) no more than 21 days ago.
• Has not yet begun but will begin standard monthly temozolomide therapy.
• Patient must have at least 1 formalin fixed paraffin embedded tumor tissue block representative of glioblastoma available for biomarker analysis and determination of MGMT status (if not already done). If tumor block is not available or not of adequate quality, sufficient pathology material, representative of glioblastoma, must be available.
• Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN for all subjects.
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
• Negative serum pregnancy test at screening for women of childbearing potential.
• Highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.
• International normalized ratio (INR) or PT (secs) and activated partial thromboplastin time (aPTT):
• in the absence of therapeutic intent to anticoagulate the subject: INR≤1.5 or PT ≤1.5 x ULN and aPTT ≤1.5 x ULN

You may not qualify if:

• Patients who have evidence of leptomeningeal disease.
• Known significant pulmonary, cardiovascular, hepatic disorders or any other disease that in the opinion of the investigator would be contraindicated to receive anti PD-L1 therapy such as avelumab.
• Prior treatment with bevacizumab or any checkpoint immune blockade thérapies.
• Any other concomitant immunosuppressant other than temozolamide and steroids or any recent (within 3 months) experimental therapy.
• Patients who have finished their radiotherapy course more than 3 weeks prior to Baseline.
• Prior organ transplantation, including allogeneic stem cell transplantation.
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Subjects with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease or any other autoimmune disease not requiring immunosuppressive treatment are at the investigator's discretion eligible
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
• Pregnancy or lactation.

Sponsors & Collaborators

• Clinique Neuro-Outaouais: lead

Study Sites (1)

Clinique Neuro-Outaouais

Gatineau, Quebec, J8Y 1W2, Canada

Location

Related Publications (1)

• Jacques FH, Nicholas G, Lorimer IAJ, Sikati Foko V, Prevost J, Dumais N, Milne K, Nelson BH, Woulfe J, Jansen G, Apedaile BE. Avelumab in newly diagnosed glioblastoma. Neurooncol Adv. 2021 Aug 25;3(1):vdab118. doi: 10.1093/noajnl/vdab118. eCollection 2021 Jan-Dec.

  PMID: 34604752 DERIVED

Related Links

• GBM clinical trial website

MeSH Terms

Interventions

avelumab

Results Point of Contact

• Title: Dr Francois Jacques
• Organization: Clinique Neuro-Outaouais

francois.jacques@neuro-outaouais.ca

819-777-2500

Study Officials

• François Jacques, MD

  Clinique Neuro-Outaouais

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: neurologist

Model Details: single center, add on, open label, single dose, single arm

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 9, 2017
• Study Start: May 19, 2017
• Primary Completion: August 9, 2021
• Study Completion: August 9, 2021
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Locations

CA (1)