Translational Study of Nivolumab in Combination With Bevacizumab for Recurrent Glioblastoma

NCT03890952 | Completed Phase 2

• 2 other identifiers: CA209-9UP2017-003925-13
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to make preliminary assessment of PD-L1 and other immune related biomarkers that might act as predictors of anti-tumor activity of Nivolumab in patients with recurrent glioblastoma

Conditions

Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Number of indels as determined using mRNA sequencing

  whole exome sequencing (WES) and mRNA sequencing on tumor versus germline-control samples. We will map cancer-specific mutations, indels, frameshifts and splice variations, and predict T cell epitopes overlapping these regions based on the patient HLA type, using available prediction tools, netMHC

  8 weeks

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  6 months

Study Arms (2)

Arm B Nivolumab and bevacizumab

EXPERIMENTAL

Nivolumab and bevacizumab in patients not undergoing salvage surgery

Drug: Nivolumab; Drug: Bevacizumab

Arm A Nivolumab and bevacizumab

EXPERIMENTAL

Nivolumab and bevacizumab in patients undergoing salvage surgery

Drug: Nivolumab; Drug: Bevacizumab

Interventions

Nivolumab DRUG

Treatment with the combination of Nivolumab and bevacizumab every 2 weeks

Also known as: Checkpoint inhibitor

Arm A Nivolumab and bevacizumab; Arm B Nivolumab and bevacizumab

Bevacizumab DRUG

Treatment with the combination of Nivolumab and bevacizumab every 2 weeks

Also known as: Angiogenesis inhibitor

Arm A Nivolumab and bevacizumab; Arm B Nivolumab and bevacizumab

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed GBM (including all histologic variants);
• Age ≥ 18 years;
• Evidence of radiological (MRI-scan) measurable recurrent progressive GBM evaluated by the Response Assessment in Neuro-Oncology (RANO) criteria;
• In arm B measurable disease according to the RANO guidelines, within 14 days of starting treatment. Measurable disease after surgery on arm A is not required with radiographic evidence of recurrent disease after treatment with temozolomide and radiotherapy;
• An interval of at least 4 weeks between prior radiotherapy or chemotherapy and enrolment on this protocol;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2;
• Life expectancy, in the opinion of the investigator \> 3 month;
• Written informed consent obtained prior to any screening procedures. Patients must be willing and able to comply with the protocol and aware of the investigational nature of this study;
• Patients must have adequate bone marrow function and organ function within 2 weeks of study treatment as defined by the following laboratory criteria;
• Hematopoietic function: total white blood cell count (WBC) ≥ 3000/mm³, absolute neutrophil count (ANC) ≥ 1500/mm³, platelet count ≥ 125,000/mm³; hemoglobin ≥ 9g/dL
• Hepatic function: bilirubin \< 1.5 times the upper limit of normal (ULN) (excluding Gilberts Syndrome, for which bilirubin must be \< 4 times ULN), ALAT \< 2.5 times ULN;
• Renal function: serum creatinine \< 1.5 ULN or estimated creatinine clearance of ≥ 50 mL/min, calculated using the formula of Cockcroft and Gault;
• APTT and INR \< normal limit
• All female patients and partners of childbearing potential must agree to use adequate birth control during study treatment and for 5 months after the last dose of study drug and have a negative serum pregnancy test at screening. Acceptable methods of contraception are oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, or a sexual partner who is surgically sterilized or post-menopausal.
• Fertile males must be willing to employ adequate means of contraception during study treatment and for 7 months after the last dose of study drug;

You may not qualify if:

• Patients must not have significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy;
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids (equivalent to max dose of 20 mg prednisolone per day) and stable for at least 5 days prior to day 1;
• Any condition (medical, social, psychological), which would prevent adequate information and follow-up;
• Any other active malignancy or previous malignancies within the last 5 years, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ;
• Uncontrolled hypertension (systolic blood pressure (BP) \> 150 mmHg and/or diastolic BP \> 100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment;
• Clinically significant peripheral vascular disease
• Evidence of bleeding diathesis, coagulopathy or taking ASA, NSAIDs or clopidogrel;
• Patients with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding);
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study;
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0;
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 0;
• Known active hepatitis A, B or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); hepatitis testing is not required;
• Known HIV infection; HIV testing is not required;
• Active infection requiring parenteral systemic antibiotics;
• Administration of a live, attenuated vaccine within 4 weeks before first dose of Nivolumab prior to surgery in Arm A or Cycle 1 Day 1 (Arm A and B) or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks before first dose of Nivolumab prior to surgery in Arm A or Cycle 1 Day 1 (Arm A and B) or at any time during the study;

Sponsors & Collaborators

• Ulrik Lassen: lead
• Herlev Hospital: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, Denmark

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Nivolumab; Bevacizumab; Angiogenesis Inhibitors

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Growth Inhibitors; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Ulrik Lassen, MD, PHD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Departmen

Model Details: Two parallel arms, non-randomized, not for comparison

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: March 26, 2019
• Study Start: October 1, 2018
• Primary Completion: February 1, 2023
• Study Completion: August 1, 2024
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

DK (1)