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

NCT02311920 | Completed Phase 1

• 4 other identifiers: NCI-2014-02404NRG-BN002PNRG-BN002_R05PAPP02U10CA180868
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 11

Brief 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. 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.

Conditions

Gliosarcoma; Supratentorial Glioblastoma

Outcome Measures

Primary Outcomes (3)

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

  The frequency and severity of toxicities will be reported.

  Up to 8 weeks

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

  The frequency and severity of toxicities will be reported.

  Up to 8 weeks

• 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.

  Up to 8 weeks

Secondary Outcomes (4)

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

  Up to 1 month post-treatment

• Biomarker analysis of immune cells within tumor samples using standard immunohistochemistry

  Up to 1 month post-treatment

• Number of patients who are alive

  1 year after the start of immunotherapy treatment

• Number of patients who are alive

  2 years after the start of immunotherapy treatment

Study Arms (3)

Arm I (temozolomide and ipilimumab)

EXPERIMENTAL

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.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Drug: Temozolomide

Arm II (temozolomide and nivolumab)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Temozolomide

Arm III (temozolomide, nivolumab, ipilimumab)

EXPERIMENTAL

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.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Temozolomide

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm I (temozolomide and ipilimumab); Arm III (temozolomide, nivolumab, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (temozolomide and ipilimumab); Arm II (temozolomide and nivolumab); Arm III (temozolomide, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Arm II (temozolomide and nivolumab); Arm III (temozolomide, nivolumab, ipilimumab)

Temozolomide DRUG

Given PO

Also known as: 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, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Arm I (temozolomide and ipilimumab); Arm II (temozolomide and nivolumab); Arm III (temozolomide, nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (11)

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

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

New York, New York, 10032, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 38874333 DERIVED

• 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.

  PMID: 29490632 DERIVED

MeSH Terms

Conditions

Gliosarcoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Temozolomide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark R Gilbert

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 9, 2014
• Study Start: April 16, 2015
• Primary Completion: December 31, 2017
• Study Completion: December 22, 2022
• Last Updated: January 10, 2023

Record last verified: 2023-01

Locations

US (11)