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NCT01125046

Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas

Completed Phase 2 Results posted Last updated 22 January 2021
What this trial tests

Phase 2 trial testing bevacizumab in Acoustic Schwannoma in 50 participants. Completed in 31 December 2018.

Timeline
17 June 2010
Primary endpoint
10 March 2014
31 December 2018

Quick facts

Lead sponsorNorthwestern University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment50
Start date17 June 2010
Primary completion10 March 2014
Estimated completion31 December 2018
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Acoustic Schwannoma or Adult Anaplastic Meningioma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) of Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab at 6 Months Primary · From the start of treatment and up until 6 months of treatment or follow up

Progression Free Survival (PFS) of patients with recurrent or progressive benign and atypical/malignant Meningiomas (grades I-III), despite prior therapy treated with bevacizumab will be defined from the time of registration to the study until the time of first documentation of progressive disease or death from any cause. Progressive disease will be assessed based on the Macdonald Criteria and is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any eval

Grade I Meningioma
GroupValue95% CI
Treatment With Bevacizumab9361 – 99
Grade II Meningioma
GroupValue95% CI
Treatment With Bevacizumab8561 – 95
Grade III Meningioma
GroupValue95% CI
Treatment With Bevacizumab5122 – 75
Grade II/III Meningioma
GroupValue95% CI
Treatment With Bevacizumab7354 – 85
Number of Patients With Each Response Secondary · From start of treatment and approximately every 8 weeks for up to approximately 5 years ( maximum duration any one patient was on treatment)

Best Response of patients treated with bevacizumab with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma will be assessed using the MacDonald Criteria. In general: Complete Response-Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients not on steroids. Partial Response-50% or greater decrease under baseline in the sum of products of perpendicular diameters of the two largest measurable lesions. No progression of evaluable disease. No new lesions. Stable

GroupValue95% CI
Treatment With Bevacizumab0
Treatment With Bevacizumab2
Treatment With Bevacizumab43
Treatment With Bevacizumab4
Safety Profile of Bevacizumab Secondary · Every 2 weeks or 3 weeks while on treatment up to 30 days after the last dose. The maximum duration any one patient was on treatment was approximately 5 years.

Safety of bevacizumab in patients with diagnosis of any of the following: meningioma, hemangiopericytoma, hemangioblastoma, acustic neuroma or schwanoma, will be assessed by collecting the number of adverse events experienced by patients that were determined to be at least possibly related to bevacaumab and assessed as a grade 3 or 4. AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. In general, AEs will be graded as follows: Grade 1 - Mild Grade 2 - Moderate Grade 3 - Severe Grade 4 - Life-threatening Grade 5 - Fatal

Hypertension
GroupValue95% CI
Treatment With Bevacizumab10
Hyponatremia
GroupValue95% CI
Treatment With Bevacizumab2
Proteinuria
GroupValue95% CI
Treatment With Bevacizumab2
Ataxia
GroupValue95% CI
Treatment With Bevacizumab1
Pancreatitis
GroupValue95% CI
Treatment With Bevacizumab1
Nausea/Vomiting
GroupValue95% CI
Treatment With Bevacizumab1
Elevated Lipase
GroupValue95% CI
Treatment With Bevacizumab1
Anemia
GroupValue95% CI
Treatment With Bevacizumab1
Levels of VEGF, VEGRfR2 and HER2 Expression in Tumor Tissue as Compared to Response Secondary · At baseline and every 8 weeks until disease progression or death. The maximum duration any one patient was on treatment was approximately 5 years.

Tissue was collected for VEGF, VEGRfR2 and HER2 at baseline. Patients underwent radiological assessments every 8 weeks during treatment to determine disease status to treatment (complete response/partial response/stable disease/progressive disease). The level of VEGF, VEGRfR2 and HER2 marker expression was compared with the response as determined at the time of disease progression or death. Immunohistochemistry (IHC) will be analyzed using blobfinder technology. Each sample was given a score for the markers expression in the tissue 1, 2 or 3 (1=+, 2=++, 3=+++, from low to high) and a percenta

#01/Partial Response : VEGF Score
GroupValue95% CI
Treatment With Bevacizumab1
#01/Partial Response : VEGF Expression
GroupValue95% CI
Treatment With Bevacizumab30
#01/Partial Response : VEGRfR2 Score
GroupValue95% CI
Treatment With Bevacizumab1
#01/Partial Response : VEGRfR2 Expression
GroupValue95% CI
Treatment With Bevacizumab10
#01/Partial Response : HER2 Score
GroupValue95% CI
Treatment With Bevacizumab0
#01/Partial Response : HER2 Expression
GroupValue95% CI
Treatment With Bevacizumab0
#02/Stable Disease : VEGF Score
GroupValue95% CI
Treatment With Bevacizumab2
#02/Stable Disease : VEGF Expression
GroupValue95% CI
Treatment With Bevacizumab80
Number of Patients Alive at 1 Year, 2 Years and 3 Years Post Treatment Initiation (Overall Survival) for Patients With Recurrent or Progressive Meningiomas Treated With Bevacizumab Secondary · At 1 year, 2 years, 3 years post treatment initiation

Overall Survival (OS) of patients with Recurrent or Progressive Meningiomas Treated with Bevacizumab will be measured from the time of treatment initiation to the study until death from any cause. The raw data of number of patients documented as being alive at 1 year, 2 year, and 3 years post treatment initiation is reported here.

At 1 year
GroupValue95% CI
Treatment With Bevacizumab43
At 2 years
GroupValue95% CI
Treatment With Bevacizumab31
At 3 years
GroupValue95% CI
Treatment With Bevacizumab16

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the time of treatment initiation until 30 days post treatment discontinuation for all patients. Range of cycles of treatment completed by patients was 1-47 where one cycle equals 28 days on bevaciumab every 2 week schedule and 42 days on bevacizumab every 3 weeks. Longest time any patient was on treatment was 5 years.. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment With Bevacizumab
Serious: 22/50 (44%)
Deaths: 30/50

Serious adverse events (30 terms)

ReactionSystemTreatment With Bevacizumab
SeizureNervous system disorders
PancreatitisGastrointestinal disorders
Anorectal InfectionInfections and infestations
Muscle weaknessMusculoskeletal and connective tissue disorders
Toxic Metabolic EncephalopathyNervous system disorders
EpistaxisGeneral disorders
AphasiaNervous system disorders
AnemiaBlood and lymphatic system disorders
FractureInjury, poisoning and procedural complications
Left sided apraxia and numbnessNervous system disorders
Muscle weakness and spasticityMusculoskeletal and connective tissue disorders
Left-sided paralysisNervous system disorders
RPLSNervous system disorders
Pain: MusculoskeletalMusculoskeletal and connective tissue disorders
Somnolence d/t narcotic overdoseNervous system disorders
Weakness- Lower ExtremityMusculoskeletal and connective tissue disorders
CNS Cebrovascular IschemiaNervous system disorders
Infection (ventriculitis)Infections and infestations
Eye InfectionInfections and infestations
HeadacheNervous system disorders
Viral BronchitisInfections and infestations
PneymocephalusNervous system disorders
Wound InfectionInfections and infestations
FallInjury, poisoning and procedural complications
Hip Prosthesis DislocationInjury, poisoning and procedural complications
Other adverse events (89 terms — click to expand)

ReactionSystemTreatment With Bevacizumab
General disorders and administration site conditions - FatigueGeneral disorders
HeadachesNervous system disorders
HypertensionVascular disorders
HyperglycemiaMetabolism and nutrition disorders
General disorders and administration site conditions - painGeneral disorders
Gastrointestinal disorders - NauseaGastrointestinal disorders
ProteinuriaRenal and urinary disorders
HypoalbuminemiaMetabolism and nutrition disorders
Nose bleedRespiratory, thoracic and mediastinal disorders
Gastrointestinal disorders - DiarrheaGastrointestinal disorders
Investigations - Aspartate aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
Investigations - Lymphocyte count decreasedInvestigations
Investigations - White blood cell decreasedInvestigations
Investigations - Alanine aminotransferase increasedInvestigations
DizzinessNervous system disorders
dysarthriaNervous system disorders
InsomniaPsychiatric disorders
General disorders and administration site conditions - Edema limbsGeneral disorders
Investigations - Platelet count decreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypoglycemiaMetabolism and nutrition disorders
Peripheral motor neuropathyNervous system disorders
SeizureNervous system disorders
HypokalemiaMetabolism and nutrition disorders
Memory impairmentNervous system disorders
Peripheral sensory neuropathyNervous system disorders
GastritisGastrointestinal disorders
General disorders and administration site conditions - Gait disturbanceGeneral disorders
Investigations - Alkaline phosphatase increasedInvestigations
Investigations - Weight lossInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Muscle weakness - extraocularMusculoskeletal and connective tissue disorders
ConfusionNervous system disorders
irregular menstrationReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders
Rash/desquamationSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
Ophthalmoplegia/diplopia (double vision)Eye disorders
Infections and infestations -Urinary tract infectionInfections and infestations

Most-reported serious reactions: Seizure, Pancreatitis, Anorectal Infection, Muscle weakness, Toxic Metabolic Encephalopathy, Epistaxis, Aphasia, Anemia.

Data from ClinicalTrials.gov NCT01125046 adverse events section.

Sponsor's own description

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progression meningiomas.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. An overview of meningiomas.
    Buerki RA, Horbinski CM, Kruser T, Horowitz PM, et al · · 2018 · cited 325× · PMID 30084265 · DOI 10.2217/fon-2018-0006
  2. Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma.
    Kaley TJ, Wen P, Schiff D, Ligon K, et al · · 2015 · cited 197× · PMID 25100872 · DOI 10.1093/neuonc/nou148
  3. Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series.
    Lou E, Sumrall AL, Turner S, Peters KB, et al · · 2012 · cited 132× · PMID 22535433 · DOI 10.1007/s11060-012-0861-0
  4. Meningioma: A Review of Clinicopathological and Molecular Aspects.
    Huntoon K, Toland AMS, Dahiya S. · · 2020 · cited 96× · PMID 33194703 · DOI 10.3389/fonc.2020.579599
  5. Bevacizumab treatment for meningiomas in NF2: a retrospective analysis of 15 patients.
    Nunes FP, Merker VL, Jennings D, Caruso PA, et al · · 2013 · cited 71× · PMID 23555840 · DOI 10.1371/journal.pone.0059941
  6. Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma.
    Furtner J, Schöpf V, Seystahl K, Le Rhun E, et al · · 2016 · cited 54× · PMID 26354929 · DOI 10.1093/neuonc/nov183
  7. NF2/merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations.
    Schroeder RD, Angelo LS, Kurzrock R. · · 2014 · cited 41× · PMID 24393766 · DOI 10.18632/oncotarget.1557
  8. New developments in neurofibromatosis type 2 and vestibular schwannoma.
    Ren Y, Chari DA, Vasilijic S, Welling DB, et al · · 2021 · cited 39× · PMID 33604573 · DOI 10.1093/noajnl/vdaa153

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01125046.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing