Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma

NCT03743662 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-400
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Glioblastoma

Keywords

WHO grade IV; IDH wildtype; MGMT hypermethylation; 18-400; nivolumab; recurrent glioblastoma; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (3)

• 6 month progression-free survival

  6 months

• Median progression-free survival

  2 years

• Objective response rate

  2 years

Study Arms (2)

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

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.

Radiation: Re-irradiation (RT); Drug: Bevacizumab; Drug: Nivolumab; Procedure: Re-resection

Interventions

Bevacizumab DRUG

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.

Recurrent Glioblastoma, No Surgery; Recurrent Glioblastoma, Surgery

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.

Recurrent Glioblastoma, No Surgery; Recurrent Glioblastoma, Surgery

Nivolumab DRUG

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.

Recurrent Glioblastoma, No Surgery; Recurrent Glioblastoma, Surgery

Re-resection PROCEDURE

Re-resection will be performed in the surgical arm at day 14 (+/- 5 days).

Recurrent Glioblastoma, Surgery

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (11)

Hartford Healthcare (Data Collection)

Hartford, Connecticut, 06102, United States

Location

Indiana University (Data Collection Only)

Indianapolis, Indiana, 46202, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Lehigh Valley Health Network (Data Collection Only)

Allentown, Pennsylvania, 18103, United States

Location

University of Vermont Medical Center (Data Collection Only)

Burlington, Vermont, 05401, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Glioblastoma

Interventions

Re-Irradiation; Bevacizumab; Nivolumab

Condition Hierarchy (Ancestors)

Astrocytoma; 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)

Radiotherapy; Therapeutics; Retreatment; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Grommes, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 16, 2018
• Study Start: November 12, 2018
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (11)