GlioblastomaPhase 2NCT03743662
Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
A Phase 2 study testing Re-irradiation (RT), Bevacizumab and Nivolumab in people with Glioblastoma, run by Memorial Sloan Kettering Cancer Center at 11 sites in United States.
Trial summary
This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Re-irradiation (RT), Bevacizumab and Nivolumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 11 sitesUnited States
- Study dates
- 12 Nov 2018to Nov 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing
- MGMT hypermethylation in archival tumor biopsy, determined by any CLIAapproved, DNA-based assay
- Prior maximal feasible surgical resection of biopsy
- Prior treatment with radiation and temozolomide chemotherapy
- Pathologic and/or Radiographic evidence of recurrent disease
- Circumscribed enhancing tumor ≤ 5.0 cm in largest diameter (T1 post contrast)
Show all 20Show fewer
- 1 prior course of radiation therapy
- Age ≥ 18 years
- Karnofsky performance status ≥ 70% or ECOG 0 or 1
- Adequate bone marrow function
- Hemoglobin ≥ 10g/dL
- Absolute neutrophil count ≥ 1,500/mm 3
- Absolute lymphocyte count ≥ 200/mm 3
- Platelet count ≥ 100,000/mm3
- Adequate liver function
- Bilirubin <1.5 times upper limit normal (ULN)
- AST and ALT ≤ 3 times ULN
- Alkaline phosphatase ≤ 2 times ULN
- Adequate renal function
- BUN and Creatinine <1.5 times ULN
Who cannot join
- Infratentorial location of the recurrence
- IDH mutated glioblastoma
- More than one prior tumor recurrence after standard first-line therapy
- Prior radiation to the brain within ≤ 4 months
- Circumscribed enhancing tumor >5.0 cm in largest diameter (T1 post contrast)
- Pulmonary embolus or deep vein thrombosis within preceding 2 months
Show all 25Show fewer
- Grade 2 or greater congestive heart failure
- Unstable angina, myocardial infarction within past 12 months
- Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
- Nonhealing wound, ulcer or bone fracture
- Prior spontaneous CNS hemorrhage (as determined from clinical history, CT, or MRI)
- Uncontrollable hypertension
- Requiring escalating or chronic supraphysiologic doses of corticosteroids (> 4 mg dexamethasone daily) for control of disease at the time of registration
- Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent.
- Previous or current treatment with bevacizumab
- Hypersensitivity to nivolumab or bevacizumab or any of its excipients
- Diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Known history of active TB (Bacillus Tuberculosis)
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Active infection requiring systemic therapy.
- Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Unable to undergo MRI of the brain (i.e. pacemaker or any other contraindication for MRIs).
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Lehigh Valley Health Network (Data Collection Only)
Allentown, Pennsylvania, 18103
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
University of Vermont Medical Center (Data Collection Only)
Burlington, Vermont, 05401
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Hartford Healthcare (Data Collection)
Hartford, Connecticut, 06102
Indiana University (Data Collection Only)
Indianapolis, Indiana, 46202
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: A Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.
- Conditions
- Glioblastoma
- Being tested
- Re-irradiation (RT), Bevacizumab, Nivolumab, Re-resection
- Keywords
- WHO grade IV, IDH wildtype, MGMT hypermethylation, 18-400, nivolumab, recurrent glioblastoma, Memorial Sloan Kettering Cancer Center
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Re-irradiation (RT)Radiation
Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.
BevacizumabDrug
Bevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician.
NivolumabDrug
Nivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation.
Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death.
Re-resectionProcedure or surgery
Re-resection will be performed in the surgical arm at day 14 (+/- 5 days).
| Study group | Role | What they receive |
|---|---|---|
| Recurrent Glioblastoma, No Surgery | Experimental | One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan Receives: Radiation: Re-irradiation (RT); Drug: Bevacizumab; Drug: Nivolumab |
| Recurrent Glioblastoma, Surgery | Experimental | The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment. Receives: Radiation: Re-irradiation (RT); Drug: Bevacizumab; Drug: Nivolumab; Procedure: Re-resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
in participants with recurrent glioblastoma (first recurrence)treated with re-irradiation with concurrent nivolumab (as well as bevacizumab if the investigator feels that the patient benefits from the addition) followed by adjuvant nivolumab in two parallel cohorts.
Measured: 2 years
Secondary outcomes (3)
6 month progression-free survival
Measured: 6 months
Median progression-free survival
Measured: 2 years
Objective response rate
ORR using the iRANO criteria
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start12 Nov 2018
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christian Grommes, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03743662
- Sponsor's protocol ID
- 18-400
- Status last verified
- Jan 2026
- First submitted
- 13 Nov 2018
- Last updated
- 7 Jan 2026
- Results posted
- No
- 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 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
- ClinicalTrials.gov ID
- NCT03743662
- Acronym / sponsor ID
- 18-400
- Conditions
- Glioblastoma
- Keywords
- WHO grade IV, IDH wildtype, MGMT hypermethylation, 18-400, nivolumab, recurrent glioblastoma, Memorial Sloan Kettering Cancer Center
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 16 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recurrent Glioblastoma, No Surgery | Experimental | Radiation: Re-irradiation (RT), Drug: Bevacizumab, Drug: NivolumabOne cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan |
| Recurrent Glioblastoma, Surgery | Experimental | Radiation: Re-irradiation (RT), Drug: Bevacizumab, Drug: Nivolumab, Procedure: Re-resectionThe second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing
- MGMT hypermethylation in archival tumor biopsy, determined by any CLIAapproved, DNA-based assay
- Prior maximal feasible surgical resection of biopsy
- Prior treatment with radiation and temozolomide chemotherapy
- Pathologic and/or Radiographic evidence of recurrent disease
Key exclusion criteria (25 listed)
- Infratentorial location of the recurrence
- IDH mutated glioblastoma
- More than one prior tumor recurrence after standard first-line therapy
- Prior radiation to the brain within ≤ 4 months
- Circumscribed enhancing tumor >5.0 cm in largest diameter (T1 post contrast)
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 |
|---|---|---|
| Re-irradiation (RT)Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period. | Radiation | Recurrent Glioblastoma, No Surgery, Recurrent Glioblastoma, Surgery |
| BevacizumabBevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician. | Drug | Recurrent Glioblastoma, No Surgery, Recurrent Glioblastoma, Surgery |
| NivolumabNivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation. Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death. | Drug | Recurrent Glioblastoma, No Surgery, Recurrent Glioblastoma, Surgery |
| Re-resectionRe-resection will be performed in the surgical arm at day 14 (+/- 5 days). | Procedure or surgery | Recurrent Glioblastoma, Surgery |
Primary outcome
Overall survival
Time frame: 2 years
in participants with recurrent glioblastoma (first recurrence)treated with re-irradiation with concurrent nivolumab (as well as bevacizumab if the investigator feels that the patient benefits from the addition) followed by adjuvant nivolumab in two parallel cohorts.
3 secondary outcomes
6 month progression-free survival
Time frame: 6 months
Median progression-free survival
Time frame: 2 years
Objective response rate
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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.
Christian Grommes, MD principal investigator
Memorial Sloan Kettering Cancer Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Re-irradiation (RT), Bevacizumab and Nivolumab in people with Glioblastoma, run by Memorial Sloan Kettering Cancer Center 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 20 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 7 Jan 2026. 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 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?
This study is still under way. Results are not available in the source record yet.
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?
Overall survival (time frame: 2 years). 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 7 Jan 2026.