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GliosarcomaPhase 1NCT02311920

Ipilimumab and/or Nivolumab in Combination With Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

A Phase 1 study testing Ipilimumab, Laboratory Biomarker Analysis and Nivolumab in people with Gliosarcoma and Supratentorial Glioblastoma, run by National Cancer Institute (NCI) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the safety and best dose of ipilimumab, nivolumab, or both in combination with temozolomide in treating patients with newly diagnosed glioblastoma or gliosarcoma. Monoclonal antibodies, such as ipilimumab and nivolumab, may block tumor growth in different ways by targeting certain cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gliosarcoma, Supratentorial Glioblastoma
What is being tested?
Ipilimumab, Laboratory Biomarker Analysis and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
11 sitesUnited States
Study dates
16 Apr 2015to 22 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report
  • 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
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  • 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

Who cannot join

  • Definitive clinical or radiologic evidence of progressive disease
  • 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
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  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase I Study of Ipilimumab, Nivolumab, and the Combination in Patients With Newly Diagnosed Glioblastoma

This phase I trial studies the safety and best dose of ipilimumab, nivolumab, or both in combination with temozolomide in treating patients with newly diagnosed glioblastoma or gliosarcoma. Monoclonal antibodies, such as ipilimumab and nivolumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which combination is a better treatment for glioblastoma or gliosarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Ipilimumab, Laboratory Biomarker Analysis, Nivolumab, Temozolomide
Medical subject headings
Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

  • TemozolomideDrug

    Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831

    Given PO

Study groups in NCT02311920
Study groupRoleWhat they receive
Arm I (temozolomide and ipilimumab)ExperimentalWithin 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.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Drug: Temozolomide
Arm II (temozolomide and nivolumab)ExperimentalWithin 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Temozolomide
Arm III (temozolomide, nivolumab, ipilimumab)ExperimentalWithin 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.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immune-related dose-limiting toxicities for the single-agent treatment with ipilimumab

    The frequency and severity of toxicities will be reported.

    Measured: Up to 8 weeks

  2. Immune-related dose-limiting toxicities for the single-agent treatment with nivolumab

    The frequency and severity of toxicities will be reported.

    Measured: Up to 8 weeks

  3. Immune-related dose-limiting toxicities for the combination of ipilimumab and nivolumab when given with temozolomide

    The frequency and severity of toxicities will be reported.

    Measured: Up to 8 weeks

Secondary outcomes (4)

  1. Incidence of adverse events, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Will 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.

    Measured: Up to 1 month post-treatment

  2. Biomarker analysis of immune cells within tumor samples using standard immunohistochemistry

    The results of this battery of assays will be used to obtain pilot data and an assessment of feasibility in obtaining reproducible results in preparation for a subsequent randomized, statistically powered comparative clinical trial.

    Measured: Up to 1 month post-treatment

  3. Number of patients who are alive

    The number of patients who are alive at 1 year will be reported.

    Measured: 1 year after the start of immunotherapy treatment

  4. Number of patients who are alive

    The number of patients who are alive at 2 years will be reported.

    Measured: 2 years after the start of immunotherapy treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2014 (estimated)
  2. Study start16 Apr 2015
  3. Primary completion31 Dec 2017
  4. Study completion22 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02311920
Sponsor's protocol ID
NCI-2014-02404
Other IDs
NCI-2014-02404, NRG-BN002, PNRG-BN002_R05PAPP02, NRG-BN002, NRG-BN002, U10CA180868
Status last verified
Jan 2023
First submitted
8 Dec 2014
Last updated
10 Jan 2023
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 38874333

  • 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.

    PubMed 29490632

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab, Laboratory Biomarker Analysis and Nivolumab in people with Gliosarcoma and Supratentorial Glioblastoma, run by National Cancer Institute (NCI) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune-related dose-limiting toxicities for the single-agent treatment with ipilimumab (time frame: Up to 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02311920, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2023.

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