- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03743662
Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
A Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Connecticut
-
Hartford, Connecticut, United States, 06102
- Hartford Healthcare (Data Collection)
-
-
Florida
-
Miami, Florida, United States, 33143
- Miami Cancer Institute Baptist Health South Florida (Data Collection Only)
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University (Data Collection Only)
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Memorial Sloan Kettering Basking Ridge
-
Middletown, New Jersey, United States, 07748
- Memorial Sloan Kettering Monmouth
-
Montvale, New Jersey, United States, 07645
- Memorial Sloan Kettering Bergen
-
-
New York
-
Commack, New York, United States, 11725
- Memorial Sloan Kettering Commack
-
Harrison, New York, United States, 10604
- Memorial Sloan Kettering Westchester
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
Uniondale, New York, United States, 11553
- Memorial Sloan Kettering Nassau
-
-
Pennsylvania
-
Allentown, Pennsylvania, United States, 18103
- Lehigh Valley Health Network (Data Collection Only)
-
-
Vermont
-
Burlington, Vermont, United States, 05401
- University of Vermont Medical Center (Data Collection Only)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Recurrent Glioblastoma, No Surgery
One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
|
Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.
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.
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. |
Experimental: Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
|
Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.
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.
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-resection will be performed in the surgical arm at day 14 (+/- 5 days).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
6 month progression-free survival
Time Frame: 6 months
|
6 months
|
|
Median progression-free survival
Time Frame: 2 years
|
2 years
|
|
Objective response rate
Time Frame: 2 years
|
ORR using the iRANO criteria
|
2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Christian Grommes, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Nivolumab
- Bevacizumab
Other Study ID Numbers
- 18-400
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Glioblastoma
-
Celldex TherapeuticsCompletedGlioblastoma | Gliosarcoma | Recurrent Glioblastoma | Small Cell Glioblastoma | Giant Cell Glioblastoma | Glioblastoma With Oligodendroglial Component | Relapsed GlioblastomaUnited States
-
Juan M Garcia-GomezHospital Universitario 12 de Octubre; Hospital Clínico Universitario de ValenciaRecruitingGlioblastoma | Glioblastoma Multiforme | High Grade Glioma | Astrocytoma, Grade IV | Glioblastoma, IDH-mutant | Glioblastoma, IDH-wildtype | Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype | Glioblastoma IDH (Isocitrate Dehydrogenase) MutantSpain
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States, Belgium, Switzerland, Germany, Netherlands
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Recurrent Glioblastoma | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of Brain | Astrocytoma of Brain | Astrocytoma, MalignantUnited States, Germany, Netherlands, Switzerland, Belgium
-
Leland MethenyNational Cancer Institute (NCI)RecruitingGlioblastoma Multiforme | Supratentorial Gliosarcoma | Glioblastoma Multiforme, Adult | Supratentorial GlioblastomaUnited States
-
Northwestern UniversityAgenus Inc.; CarTheraRecruitingGlioblastoma Multiforme | Gliosarcoma | Newly Diagnosed Glioblastoma | Glioblastoma, Isocitric Dehydrogenase (IDH)-WildtypeUnited States
-
University Hospital, GenevaActive, not recruitingGlioblastoma Multiforme | Glioblastoma Multiforme of Brain | Glioma of Brain | Glioblastoma, AdultSwitzerland
-
Milton S. Hershey Medical CenterRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
-
Northwestern UniversityNational Cancer Institute (NCI)RecruitingGlioblastoma | Astrocytoma | Recurrent Glioblastoma | MGMT-Unmethylated Glioblastoma | Glioblastoma, IDH-WildtypeUnited States
-
Milton S. Hershey Medical CenterNational Cancer Institute (NCI)RecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
Clinical Trials on Re-irradiation (RT)
-
University Hospital HeidelbergRecruitingLocally Advanced Head-and-Neck CancerGermany
-
Memorial Sloan Kettering Cancer CenterActive, not recruiting
-
University of CalgaryRecruitingRecurrent or Progressive Diffuse Intrinsic Pontine GliomaCanada, Australia, New Zealand
-
Medical College of WisconsinRecruiting
-
Rigshospitalet, DenmarkKarolinska University Hospital; Aarhus University Hospital; Sahlgrenska University... and other collaboratorsNot yet recruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Diffuse Glioma | Pontine Tumors | Brain Tumor, Pediatric | Thalamic Tumor
-
University College, LondonGlaxoSmithKlineWithdrawnRecurrent Glioblastoma
-
Changhai HospitalActive, not recruitingPancreatic CancerChina
-
Istituto Scientifico Romagnolo per lo Studio e...Recruiting
-
Hadassah Medical OrganizationCompletedPediatric Malignant Brain Tumor -Diffuse Intrinsic Pontine GliomaIsrael
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI); NRG OncologyCompletedLung CancerUnited States, Canada, Israel