Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma

Phase 2

Active, not recruiting

• Conditions: Glioblastoma
• Interventions: Radiation: Re-irradiation (RT); Drug: Bevacizumab; Drug: Nivolumab; Procedure: Re-resection

• Registration Number: NCT03743662
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-11-12
• Study First Submitted: 2018-11-13
• Study First Submitted QC: 2018-11-15
• Study First Posted: 2018-11-16
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-07
• Primary Completion: 2025-11
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 39

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% 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

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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)
• 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Recurrent Glioblastoma, No Surgery	Re-irradiation (RT)	One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Recurrent Glioblastoma, No Surgery	Bevacizumab	One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Recurrent Glioblastoma, Surgery	Re-irradiation (RT)	The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Recurrent Glioblastoma, Surgery	Bevacizumab	The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Recurrent Glioblastoma, Surgery	Re-resection	The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Recurrent Glioblastoma, No Surgery	Nivolumab	One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Recurrent Glioblastoma, Surgery	Nivolumab	The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.

Primary Outcome Measures

Name	Time	Method
Overall survival	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.

Secondary Outcome Measures

Name	Time	Method
6 month progression-free survival	6 months
Median progression-free survival	2 years
Objective response rate	2 years	ORR using the iRANO criteria

Trial Locations

Locations (12)

Lehigh Valley Health Network (Data Collection Only); 🇺🇸 Allentown, Pennsylvania, United States

University of Vermont Medical Center (Data Collection Only); 🇺🇸 Burlington, Vermont, United States

Miami Cancer Institute Baptist Health South Florida (Data Collection Only); 🇺🇸 Miami, Florida, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Hartford Healthcare (Data Collection); 🇺🇸 Hartford, Connecticut, United States

Memorial Sloan Kettering Bergen; 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Basking Ridge; 🇺🇸 Basking Ridge, New Jersey, United States

Indiana University (Data Collection Only); 🇺🇸 Indianapolis, Indiana, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Commack; 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Nassau; 🇺🇸 Uniondale, New York, United States