Ipilimumab and/or Nivolumab in Combination With Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
NCT ID: NCT02311920
Last Updated: 2023-01-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
32 participants
INTERVENTIONAL
2015-04-16
2022-12-22
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Association of Peripheral Blood Immunologic Response to Therapeutic Response to Adjuvant Treatment With Immune Checkpoint Inhibition (ICI) in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
NCT04817254
An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer)
NCT02617589
Ipilimumab and Nivolumab in Leptomeningeal Metastases
NCT02939300
A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients
NCT02017717
Atezolizumab in Combination With Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
NCT03174197
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. Determine the maximum safe dose of single-agent treatment with ipilimumab, nivolumab and the combination when given with temozolomide during maintenance treatment for newly diagnosed glioblastoma.
SECONDARY OBJECTIVES:
I. Collect and record the side effect profiles for single-agent treatment with ipilimumab, nivolumab, and the combination when given with temozolomide during the maintenance phase for newly diagnosed glioblastoma.
II. Perform pilot studies of immune cells within tumor samples, e.g. phenotyping tumor infiltrating lymphocytes (TILs) by interrogating tumor tissues from diagnostic tumor blocks.
III. Report the number of patients alive at 1 and 2 years after the start of single-agent treatment with ipilimumab, nivolumab, and the combination when given with temozolomide during the maintenance phase for newly diagnosed glioblastoma.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Within 5 weeks after completion of chemoradiation, patients receive temozolomide orally (PO) on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab intravenously (IV) over 90 minutes once every 4 weeks for 4 courses and then beginning 3 months after course 4 once every 3 months for 4 courses in the absence unacceptable toxicity.
ARM II: Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 60 minutes once every 2 weeks for 16 weeks and then once every 2 weeks for 48 weeks in the absence unacceptable toxicity.
ARM III: Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 90 minutes once every 4 weeks for 4 courses and nivolumab IV over 60 minutes once every 2 weeks for 64 weeks in the absence unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month, and then every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm I (temozolomide and ipilimumab)
Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 90 minutes once every 4 weeks for 4 courses and then beginning 3 months after course 4 once every 3 months for 4 courses in the absence unacceptable toxicity.
Ipilimumab
Given IV
Laboratory Biomarker Analysis
Correlative studies
Temozolomide
Given PO
Arm II (temozolomide and nivolumab)
Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 60 minutes once every 2 weeks for 16 weeks and then once every 2 weeks for 48 weeks in the absence unacceptable toxicity.
Laboratory Biomarker Analysis
Correlative studies
Nivolumab
Given IV
Temozolomide
Given PO
Arm III (temozolomide, nivolumab, ipilimumab)
Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 90 minutes once every 4 weeks for 4 courses and nivolumab IV over 60 minutes once every 2 weeks for 64 weeks in the absence unacceptable toxicity.
Ipilimumab
Given IV
Laboratory Biomarker Analysis
Correlative studies
Nivolumab
Given IV
Temozolomide
Given PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ipilimumab
Given IV
Laboratory Biomarker Analysis
Correlative studies
Nivolumab
Given IV
Temozolomide
Given PO
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* The tumor must be unifocal, confined to the supratentorial compartment and have undergone a gross total or near gross total resection; this will increase the likelihood that the patient will not require corticosteroids or develop pseudoprogression
* The formalin-fixed, paraffin-embedded (FFPE) tumor tissue block must be available to be sent for retrospective central pathology review after registration
* Patients must be registered within 35 days of completion of chemoradiation
* History/physical examination within 7 days prior to registration
* Patients must have undergone an evaluation by magnetic resonance imaging (MRI) within 35 days of completing radiation and must also be within 7 days prior to registration; MRI must NOT demonstrate tumor progression, but patients with imaging changes consistent with pseudo-progression, stable neurologic function and not needing corticosteroid treatment are eligible
* Karnofsky performance status \>= 70 within 7 days prior to registration
* Absolute neutrophil count \>= 1,500 cells/mm\^3
* Platelet count \>= 100,000 cells/mm\^3
* Hemoglobin (Hgb) \> 9 g/dL (can be achieved with transfusion)
* Blood urea nitrogen (BUN) =\< 30 mg/dl
* Serum creatinine =\< 1.7 mg/dl
* Total bilirubin (except patients with Gilbert's syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) =\< 2.0 mg/dl
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN)
* The patient must have completed chemoradiation (all cohorts) within standards of care established by prior Radiation Therapy Oncology Group (RTOG)/Network Radiotherapy Group (NRG) Oncology studies as follows:
* Radiation therapy
* Modality: either 3-dimensional (3D) or intensity-modulated radiation therapy (IMRT), or proton therapy is allowed
* Time to initiation: radiotherapy must be initiated within or equal to 42 days after surgery
* Target volumes: target volume definition will be based upon postoperative-enhanced MRI; preoperative imaging should be used for correlation and improved identification, as necessary
* Dose guidelines: the initial target volume will be treated to 46 Gray (Gy) in 23 fractions; after 46 Gy, the cone-down or boost volume will be treated to a total of 60 Gy, with seven additional fractions of 2 Gy each (14 Gy boost dose)
* Temozolomide during concomitant radiation therapy
* Temozolomide must have been administered continuously from day 1 of radiotherapy to the last day of radiation (+/- 3 days to take into consideration holidays) at a daily oral dose of 75 mg/m\^2 for a maximum of 49 days (except missed doses due to toxicity)
* The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent
* The patient must provide study-specific informed consent prior to study entry
* Echocardiogram (ECHO) cardiogram and cardiology consultation required within 7 days prior to registration for patients with a history of congestive heart failure or cardiovascular disease or history of exposure to cardiotoxic agents who are not already excluded
Exclusion Criteria
* Prior placement of Gliadel wafer or local brachytherapy
* Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
* Unstable angina within the last 6 months prior to registration
* Transmural myocardial infarction within the last 6 months prior to registration
* Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 7 days prior to registration
* New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
* History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration
* Serious and inadequately controlled cardiac arrhythmia
* Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for additional liver function tests and coagulation parameters are not required for entry into this protocol
* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
* Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded
* Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
* Pregnancy or lactating females; women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration
* History of severe hypersensitivity reaction to any monoclonal antibody
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
NRG Oncology
OTHER
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Mark R Gilbert
Role: PRINCIPAL_INVESTIGATOR
NRG Oncology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
UCSF Medical Center-Parnassus
San Francisco, California, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
M D Anderson Cancer Center
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Sloan AE, Winter K, Gilbert MR, Aldape K, Choi S, Wen PY, Butowski N, Iwamoto FM, Raval RR, Voloschin AD, Kamiya-Matsuoka C, Won M, Mehta MP. NRG-BN002: Phase I study of ipilimumab, nivolumab, and the combination in patients with newly diagnosed glioblastoma. Neuro Oncol. 2024 Sep 5;26(9):1628-1637. doi: 10.1093/neuonc/noae058.
Ranjan S, Quezado M, Garren N, Boris L, Siegel C, Lopes Abath Neto O, Theeler BJ, Park DM, Nduom E, Zaghloul KA, Gilbert MR, Wu J. Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases. BMC Cancer. 2018 Mar 1;18(1):239. doi: 10.1186/s12885-018-4131-1.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2014-02404
Identifier Type: REGISTRY
Identifier Source: secondary_id
NRG-BN002
Identifier Type: -
Identifier Source: secondary_id
PNRG-BN002_R05PAPP02
Identifier Type: -
Identifier Source: secondary_id
NRG-BN002
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-BN002
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2014-02404
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.