NCT04145115|Active Not RecruitingPhase 2FDA Drug

A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden

A Phase II Study of Checkpoint Blockade Immunotherapy in Patients With Somatically Hypermutated Recurrent WHO Grade 4 Glioma

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2019-07242A071702U10CA180821

Study Type

interventional

Target

Locations

2 countries

Sites

416

Timeline

RegisteredOct 2019

StartedDec 2020

CompletionDec 2026

Brief Summary

This phase II trial studies the effect of immunotherapy drugs (ipilimumab and nivolumab) in treating patients with glioma that has come back (recurrent) and carries a high number of mutations (mutational burden). Cancer is caused by changes (mutations) to genes that control the way cells function. Tumors with high number of mutations may respond well to immunotherapy. Immunotherapy with monoclonal antibodies such as ipilimumab and nivolumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving ipilimumab and nivolumab may lower the chance of recurrent glioblastoma with high number of mutations from growing or spreading compared to usual care (surgery or chemotherapy).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

8mo left

Started Dec 2020

Longer than P75 for phase_2

Geographic Reach

2 countries

416 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6 years study duration

Study Progress89%

Dec 2020Dec 2026

First Submitted

Initial submission to the registry

October 29, 2019

Completed

1 day until next milestone

First Posted

Study publicly available on registry

October 30, 2019

Completed

1.2 years until next milestone

Study Start

First participant enrolled

December 24, 2020

Completed

6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

May 4, 2026

Status Verified

February 1, 2026

Enrollment Period

6 years

First QC Date

October 29, 2019

Last Update Submit

May 1, 2026

Conditions

Astrocytoma, IDH-Mutant, Grade 4 Glioblastoma, IDH-Wildtype Secondary Glioblastoma Diffuse Glioma

Outcome Measures

Primary Outcomes (1)

Overall response rate
Assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). The proportion of patients who have a confirmed tumor response will be computed as the number of patients with a confirmed complete response or confirmed partial response as determined by RANO criteria divided by the number of evaluable patients, which are eligible patients who have measurable disease and completed one cycle of treatment. Will be estimated with a binomial point estimate that will be computed as the number of responses divided by the number of evaluable patients. Exact 95% binomial confidence intervals will be generated and reported.
Up to 32 months

Secondary Outcomes (3)

Overall survival (OS)
From the time of treatment initiation until death from any cause, assessed up to 3 years
Progression-free survival (PFS)
From the time of treatment initiation until disease progression as measured using RANO criteria or death, whichever occurs first, assessed up to 3 years
Incidence of adverse events (AEs)
Up to 3 years

Study Arms (1)

Treatment (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the study.

Biological: IpilimumabProcedure: Magnetic Resonance ImagingBiological: Nivolumab

Interventions

IpilimumabBIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Treatment (nivolumab, ipilimumab)

Magnetic Resonance ImagingPROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (nivolumab, ipilimumab)

NivolumabBIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (nivolumab, ipilimumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

PRE-REGISTRATION ELIGIBILITY CRITERIA:
Histologically confirmed glioblastoma (World Health Organization \[WHO\] grade IV) presenting at first or second recurrence including secondary glioblastoma
Glioblastoma IDH-wildtype central nervous system (CNS) WHO grade 4
Diffuse, astrocytic glioma IDH-wildtype with one or more of the following histological or genetic features: microvascular proliferation, necrosis, TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes
Astrocytoma, IDH-mutant CNS WHO grade 4
Diffuse astrocytic glioma IDH-mutant (with frequent ATRX and/or TP53 mutation and absence of 1p/19q codeletion), with necrosis and/or microvascular proliferation or one with lower grade histological features displaying homozygous deletion of CDKN2A and/or CDKN2B
NOTE: The eligibility criteria were changed to include the new diagnostic language from the WHO 2021 pathology classification change. The above diagnoses therefore reflect the change and include the entities that were previously eligible but now carry updated pathologic classification
Presence of measurable disease, as defined by a bidimensionally measurable lesion on magnetic resonance imaging (MRI) with a minimum diameter of 10 mm in both dimensions, prior to resection or biopsy of recurrent tumor
Tissue available from surgical resection or biopsy of recurrent tumor =\< 28 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor =\< 28 days after pre-registration
Does not require \> 4 mg dexamethasone beyond the perioperative period defined as the time =\< 2 weeks after surgical procedure
No active autoimmune disease or history of autoimmune disease
These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, 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 because of the risk of recurrence or exacerbation of disease
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
No prior treatment with checkpoint blockade therapies (anti-CTLA4, anti-PD1/PD-L1) or bevacizumab
No prior treatment with laser ablation at the time of recurrent tumor tissue sampling. Patients who have previously undergone laser ablation \>= 4 months prior to recurrent tumor tissue sampling can be included
+11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (416)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC