Clinical Trials /

Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma

NCT03743662

Description:

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.

Related Conditions:
  • Glioblastoma
  • Glioblastoma, IDH- Wildtype
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 18-400
  • NCT ID: NCT03743662

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
BevacizumabRecurrent Glioblastoma, No Surgery
NivolumabRecurrent Glioblastoma, No Surgery

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Recurrent Glioblastoma, No SurgeryExperimentalOne cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
  • Bevacizumab
  • Nivolumab
Recurrent Glioblastoma, SurgeryExperimentalThe second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
  • Bevacizumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  1 prior course of radiation therapy

          -  Age ≥ 18 years

          -  Karnofsky performance status ≥ 70%

          -  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

        Exclusion Criteria:

          -  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)

          -  Ongoing use of anticoagulative or antiplatelet therapy

          -  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

          -  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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival in participants with recurrent glioblastoma (first recurrence)treated with re-irradiation with concurrent bevacizumab and nivolumab followed by adjuvant nivolumab in two parallel cohorts.
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:6 month progression-free survival
Time Frame:6 months
Safety Issue:
Description:
Measure:Median progression-free survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:ORR using the iRANO criteria

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

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

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