MGMT-unmethylated Glioblastoma (GBM)Phase 2NCT03367715
Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma
A Phase 2 study testing Nivolumab, Ipilimumab and Radiation Therapy (RT) in people with MGMT-unmethylated Glioblastoma (GBM) and GBM, run by NYU Langone Health at 1 site in United States.
Trial summary
This is a single arm, open-label, phase II trial of nivolumab, ipilimumab and short-course radiation therapy in adult patients with newly diagnosed, MGMT unmethylated GBM with the primary objective of determining the overall survival at 1 year. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- MGMT-unmethylated Glioblastoma (GBM), GBM
- What is being tested?
- Nivolumab, Ipilimumab and Radiation Therapy (RT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2018to 17 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects aged ≥18 years.
- Histopathological evidence of glioblastoma or gliosarcoma, WHO grade IV.
- Tumor MGMT promoter DNA not methylated (i.e., unmethylated) by central testing.
- Maximal tumor diameter (including residual tumor and resection cavity if subjects had tumor resection rather than only stereotactic biopsy) of 6.6 cm or less. Maximal tumor size allowed is derived from an estimated maximal radiotherapy planning target volume (PTV) of 150 cm3.
- Subjects must not have received any prior standard or investigational anti-tumor therapy other than surgery and must not intend to receive any standard or investigational anti-tumor therapy other than the study regimen.
- Karnofsky performance status (Appendix 2) of ≥60.
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- Availability of a paraffin-embedded or frozen tumor-tissue block with a minimum of 1 cm2 of tumor surface area, or 20 unstained slides from the glioblastoma tissue specimen if a tumor block cannot be submitted.
- Subjects must start study agent within 6 weeks from the first diagnostic surgery for glioblastoma.
- An interval of at least 2 weeks for surgical resection and 1 week for stereotactic biopsy from the start of study treatment.
- A contrast-enhanced MRI must be obtained within 7 days of the first dose of study treatment.
- Adequate hematologic, hepatic, and renal function defined by
- White blood cell count ≥ 2.0 x 109/L
- Absolute neutrophil count ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin > 9 g/dL
- Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min according to the Cockcroft-Gault formula or local institutional standard method
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
- Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Women of child-bearing potential (WOCBP) and men able to father a child must agree to use highly effective contraception (any contraceptive method with a failure rate of less than 1% per year) while on study drug and for 23 weeks (for women) or 31 weeks (for men) after the last dose of study drug.
- WOCBP must have a negative serum or urine pregnancy test within 24 hours of initiation of study drug.
- WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be defined as post-menopausal.
- WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.
- Highly effective contraceptive measures include: stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence.
- Contraception is not required for men with documented vasectomy.
- Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
- Women must not be breastfeeding.
- Willing to and capable of providing written informed consent prior to any study related procedures.
- Ability and willingness to comply with all study requirements, including scheduled visits, treatment plans, laboratory tests, and other study-related procedures.
Who cannot join
- Prior use of any standard or investigational anti-tumor therapy other than surgery
- Planned participation in another study of an investigational agent or investigational device or planned use of any other agent or therapeutic device intended for therapy of glioma.
- Prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
- Primary brainstem or spinal cord tumor.
- Diffuse leptomeningeal gliomatosis.
- Known mutation of the IDH1 or IDH2 genes in the tumor, since glioblastomas with these mutations have different biology and are associated with improved prognosis.
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- Systemic treatment with either immunosuppressive doses of corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
- Subjects on a standard high-dose steroid taper after craniotomy or stereotactic biopsy may have received a higher dose of corticosteroids within 14 days of registration, however must be at a dose < 10 mg daily prednisone or bioequivalent per day within 5 days prior to initiation of study drug.
- Administration of steroids through a route known to result in a minimal systemic exposure [i.e., intranasal, intraocular, inhaled, topical, or local injection (e.g., intra-articular injection) corticosteroids (<5% of body surface area)] are permitted in the absence of active autoimmune disease.
- Subjects requiring adrenal replacement with corticosteroids are eligible if the steroids are at doses ≤ 10 mg prednisone or bioequivalent per day in the absence of active autoimmune disease.
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed.
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. The following conditions are not exclusions (subjects with the following conditions are permitted):
- a.Patients with diabetes type I, vitiligo, residual hypo- or hyperthyroidism due to autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic immunosuppressive treatment, or autoimmune conditions not expected to recur in the absence of an external trigger.
- Prior organ transplantation, including allogeneic stem cell transplantation.
- Known history of, or any evidence of active, non-infectious pneumonitis within the last 5 years.
- Known severe (NCI-CTCAE v4.03 Grade 3 or 4) infusion-related allergy or acute hypersensitivity reaction attributed to any monoclonal antibody, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
- Unable tolerate an MRI, or have a contraindication to MRI.
- Active infection requiring systemic therapy.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
- Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (HCV antibody) indicating acute or chronic infection.
- Vaccination within 4 weeks of the first dose of study drug and while on trials is prohibited except for administration of inactivated vaccines. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Patients with another active cancer [excluding basal cell carcinoma, cervical carcinoma in situ or melanoma in situ]. Prior history of other cancer is allowed, as long as there was no active disease within the prior 2 years.
- All other unstable, severe, or chronic medical or psychiatric conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, recent (within the past year) or active suicidal ideation or behavior, known alcohol or drug abuse, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine
New York, New York, 10016
About this study
Official title: A Phase II, Open-label, Single Arm Trial of Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma
This is a single arm, open-label, phase II trial of nivolumab, ipilimumab and short-course radiation therapy in adult patients with newly diagnosed, MGMT unmethylated GBM with the primary objective of determining the overall survival at 1 year.
- Conditions
- MGMT-unmethylated Glioblastoma (GBM), GBM
- Being tested
- Nivolumab, Ipilimumab, Radiation Therapy (RT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
study treatment on Day 1 with one dose of nivolumab 3 mg/kg
IpilimumabDrug
study treatment on Day 1 with one dose of ipilimumab 1mg/kg
Radiation Therapy (RT)Radiation
total dose of 30 Gy, given in 5 consecutive fractions of 6 Gy each fraction.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab + Ipilimumab + Short-course radiation therapy | Experimental | within 6 weeks of the first diagnostic surgery for glioblastoma, all subjects will initiate study treatment on Day 1 Receives: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiation Therapy (RT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year Overall Survival (OS)
Survival rate is defined as the percentage of participants who survived at 1 year (from either the date of diagnosis or the start of treatment for a disease)
Measured: 1 year
Secondary outcomes (2)
Median Overall Survival (OS)
Median survival rate of evaluable participants will be reported in months of survival
Measured: 3 years
Median Progression Free Survival (PFS)
The length of time during and after the treatment that a patient lives with the disease but it does not get worse.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2017
- Study start7 Feb 2018
- Primary completion20 May 2021
- Study completion17 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MGMT-unmethylated Glioblastoma (GBM)Studies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Chi, MD, Principal investigator, NYU Langone HealthSylvia Kurz, MD, Principal investigator, NYU Langone HealthErik Sulman, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03367715
- Sponsor's protocol ID
- 17-00218
- Status last verified
- Jun 2022
- First submitted
- 5 Dec 2017
- Last updated
- 1 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Single Arm Trial of Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma
- ClinicalTrials.gov ID
- NCT03367715
- Acronym / sponsor ID
- 17-00218
- Conditions
- MGMT-unmethylated Glioblastoma (GBM), GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 20 May 2021 (actual)
- Study completion
- 17 Mar 2022 (actual)
- First posted
- 11 Dec 2017 (actual)
- Results
- Posted 1 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, open-label, phase II trial of nivolumab, ipilimumab and short-course radiation therapy in adult patients with newly diagnosed, MGMT unmethylated GBM with the primary objective of determining the overall survival at 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + Ipilimumab + Short-course radiation therapy | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Radiation: Radiation Therapy (RT)within 6 weeks of the first diagnostic surgery for glioblastoma, all subjects will initiate study treatment on Day 1 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Male or female subjects aged ≥18 years.
- Histopathological evidence of glioblastoma or gliosarcoma, WHO grade IV.
- Tumor MGMT promoter DNA not methylated (i.e., unmethylated) by central testing.
- Maximal tumor diameter (including residual tumor and resection cavity if subjects had tumor resection rather than only stereotactic biopsy) of 6.6 cm or less. Maximal tumor size allowed is derived from an estimated maximal radiotherapy planning target volume (PTV) of 150 cm3.
- Subjects must not have received any prior standard or investigational anti-tumor therapy other than surgery and must not intend to receive any standard or investigational anti-tumor therapy other than the study regimen.
Key exclusion criteria (24 listed)
- Prior use of any standard or investigational anti-tumor therapy other than surgery
- Planned participation in another study of an investigational agent or investigational device or planned use of any other agent or therapeutic device intended for therapy of glioma.
- Prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
- Primary brainstem or spinal cord tumor.
- Diffuse leptomeningeal gliomatosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumabstudy treatment on Day 1 with one dose of nivolumab 3 mg/kg | Drug | Nivolumab + Ipilimumab + Short-course radiation therapy |
| Ipilimumabstudy treatment on Day 1 with one dose of ipilimumab 1mg/kg | Drug | Nivolumab + Ipilimumab + Short-course radiation therapy |
| Radiation Therapy (RT)total dose of 30 Gy, given in 5 consecutive fractions of 6 Gy each fraction. | Radiation | Nivolumab + Ipilimumab + Short-course radiation therapy |
Primary outcome
1-year Overall Survival (OS)
Time frame: 1 year
Survival rate is defined as the percentage of participants who survived at 1 year (from either the date of diagnosis or the start of treatment for a disease)
2 secondary outcomes
Median Overall Survival (OS)
Time frame: 3 years
Median Progression Free Survival (PFS)
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Chi, MD principal investigator
NYU Langone Health
Sylvia Kurz, MD principal investigator
NYU Langone Health
Erik Sulman, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Ipilimumab and Radiation Therapy (RT) in people with MGMT-unmethylated Glioblastoma (GBM) and GBM, run by NYU Langone Health at 1 site 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 28 inclusion and 24 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 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
1-year Overall Survival (OS) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2022.