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NCT01898130

Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy

Completed Phase 2 Results posted Last updated 17 September 2019
What this trial tests

Phase 2 trial testing bevacizumab in Metastatic Cancer in 27 participants. Completed in 5 September 2018.

Timeline
27 November 2013
Primary endpoint
23 March 2017
5 September 2018

Quick facts

Lead sponsorNorthwestern University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment27
Start date27 November 2013
Primary completion23 March 2017
Estimated completion5 September 2018
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Metastatic Cancer or Unspecified Adult Solid Tumor, Protocol Specific. 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.

Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Primary · Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.

Radiographic Response to treatment will be assessed prior to every odd-numbered cycle using CT or MRI scans until disease progression, unacceptable toxicity as assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as the number of patients with Complete Response (CR) plus those with Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.

GroupValue95% CI
Treatment (Bevacizumab)2
Progression-Free Survival (PFS) at 6 Months in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · At 6 months from treatment initiation.

Progression-Free Survival (PFS) will be measured as the time from the first dose to the first occurrence of progression or death for any reason. To estimate PFS, Kaplan-Meier curves will be calculated and PFS at 6 months will be determined from the progression-free survival curve. Progression is defined using Response Assessment in Neuro-Oncology Criteria (RANO), as a 25% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
Treatment (Bevacizumab)4625 – 67
Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · From treatment initiation, every 2 cycles (1 cycle = 28 days) until progressive disease. Range of cycles completed 1-20.

MRI or CT scans and clinical assessment will be used to measure Time to Progression which will be assessed as the time from the date of first dose to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, or early discontinuation of treatment as assessed by the RANO Criteria in those patients that experience response.

All Partial Response Patients
GroupValue95% CI
Treatment (Bevacizumab)30091 – 545
Clinical Partial Response
GroupValue95% CI
Treatment (Bevacizumab)18791 – 314
Radiological Partial Response
GroupValue95% CI
Treatment (Bevacizumab)525504 – 545
Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · From the start of treatment every 2 cycles (1 cycle =28 days) until time of response. Range of cycles completed 1-20.

MRI or CT scans and clinical assessment will be used to measure Time to Response which will be assessed as the time from the date of first dose to the date of first observed tumor response in all patients that a response is observed. Response to treatment will be assessed using the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as either Complete Response (CR) or a Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of tar

All Partial Response Patients
GroupValue95% CI
Treatment (Bevacizumab)7353 – 116
Clinical Partial Response
GroupValue95% CI
Treatment (Bevacizumab)7853 – 116
Radiological Partial Response
GroupValue95% CI
Treatment (Bevacizumab)6255 – 69
Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · From documentation of response, every two cycles (1 cycle =28 days) until progressive disease. Range of cycles completed 1-20.

The Duration of Overall Response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) until the first date that recurrent or Progressive Disease (PD) is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Duration of response will be based on CT or MRI scans and clinical assessment performed prior to every odd-numbered cycle to detect date of first response to study treatment until date of disease progression and assessed by the Response Assessment in Neuro-Onc

All Partial Response Patients
GroupValue95% CI
Treatment (Bevacizumab)22711 – 490
Clinical Partial Response
GroupValue95% CI
Treatment (Bevacizumab)11011 – 119
Radiological Partial Response
GroupValue95% CI
Treatment (Bevacizumab)463435 – 490
Overall Survival (OS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · From start of treatment until death from any cause. Median follow up of 8 months (range 1.3 to 47.9 months)

Overall Survival (OS) will be measured as the date of first dose of bevacizumab to the date of death from any cause. To estimate OS, Kaplan-Meier curves will be calculated and OS will be determined from the overall survival curve.

GroupValue95% CI
Treatment (Bevacizumab)8.24.2 – 12.0
Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Secondary · Assessed prior to every cylcle (cycle=28 days) while on treatment through 30 days post last dose. Range of cycles 1-20.

Adverse events (AE) will be collected at the start of every cycle and graded according NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All AEs that are determined to be grade 3 or higher and at least possible related to bevacizumab will be reported for toxicity. In general AEs will be graded: Grade 1 - Mild: the event causes discomfort without disruption of normal daily activities. Grade 2 - Moderate: the event causes discomfort that affects normal daily activities. Grade 3 - Severe: the event makes the patient unable to perform normal daily activities or significan

Lymphocyte Count Decreased
GroupValue95% CI
Treatment (Bevacizumab)1
Headache
GroupValue95% CI
Treatment (Bevacizumab)1
Hypertension
GroupValue95% CI
Treatment (Bevacizumab)3
Thromboembolic Event
GroupValue95% CI
Treatment (Bevacizumab)1
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · Baseline and at Cycle 3 (1 Cycle = 28 days).

Changes in quality of life will be evaluated using questionnaires (FACT-Br) at baseline (before treatment initiation) and at cycle 3. Four FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT-G (Fact General, possible range 0 - 108) BrCS (Brain Cancer Subscale, possible range 0 - 92) TOTAL (FACT-G + BrCS, possible range 0 - 200) TOI (Trial Outcome Index = Physical Well Being \_ Functional Well Being +BrCS, possible range 0 - 148)

Baseline FACT-G
GroupValue95% CI
Treatment (Bevacizumab)83.067.7 – 105.0
Baseline BrCS
GroupValue95% CI
Treatment (Bevacizumab)64.846.0 – 87.0
Baseline TOTAL
GroupValue95% CI
Treatment (Bevacizumab)147.8124.3 – 189.0
Baseline TOI
GroupValue95% CI
Treatment (Bevacizumab)106.077.0 – 139.0
Cycle 3 FACT-G
GroupValue95% CI
Treatment (Bevacizumab)75.950.8 – 99.0
Cycle 3 BrCS
GroupValue95% CI
Treatment (Bevacizumab)62.836.1 – 80.0
Cycle 3 TOTAL
GroupValue95% CI
Treatment (Bevacizumab)138.793.8 – 178.0
Cycle 3 TOI
GroupValue95% CI
Treatment (Bevacizumab)99.457.1 – 130.0
Response Rate in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.

Response Rate is defined as all patients with Complete Response plus those with Partial Response as assessed by Response Assessment in Neuro-Oncology (RANO) Criteria of CT or MRI scans for target lesions combined with clinical assessment. Generally RANO Response definitions are as follows: CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.

GroupValue95% CI
Treatment (Bevacizumab)6
Progression Free Survival (PFS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Secondary · From treatment initiation and every two cycles (1 cycle = 28 days) until disease progression. Median follow up of 8 months (range 1.3 to 47.9 months).

Progression Free Survival (PFS) is measured from the time of treatment initiation until documentation of progressive disease or death from any cause. To estimate PFS, Kaplan-Meier curves will be calculated and PFS will be determined from the progression-free survival curve. Progression is defined using Response Assessment in Neuro-Oncology Criteria (RANO), as a 25% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

GroupValue95% CI
Treatment (Bevacizumab)4.33.3 – 7.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Bevacizumab)
Serious: 19/27 (70%)
Deaths: 24/27

Serious adverse events (21 terms)

ReactionSystemTreatment (Bevacizumab)
Disease ProgressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
SeizureNervous system disorders
Clinical DeclineNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HeadacheNervous system disorders
Febrile NeutropeniaBlood and lymphatic system disorders
Viral GastroenteritisInfections and infestations
Pleural EffusionRespiratory, thoracic and mediastinal disorders
Transient Ischemic AttackNervous system disorders
Death due to Intracranial HemorrhageNervous system disorders
HeadacheNervous system disorders
PneumoniaInfections and infestations
Viral IllnessInfections and infestations
VomitingGastrointestinal disorders
Death NOS (Not otherwise specified)General disorders
DysarthriaNervous system disorders
ColitisGastrointestinal disorders
Blood Bilirubin IncreasedInvestigations
DyspneaRespiratory, thoracic and mediastinal disorders
Radiation EnteritisGastrointestinal disorders
ConstipationGastrointestinal disorders
Pulmonary EdemaRespiratory, thoracic and mediastinal disorders
Other adverse events (56 terms — click to expand)

ReactionSystemTreatment (Bevacizumab)
HypoalbuminemiaMetabolism and nutrition disorders
Lymphocyte Count DecreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypertensionVascular disorders
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Aspartate Aminotransferase IncreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
White Blood Cell DecreasedInvestigations
ConstipationGastrointestinal disorders
Alkaline Phosphatase IncreasedInvestigations
Platelet Count DecreasedInvestigations
Weight LossInvestigations
Alanine Aminotransferase IncreasedInvestigations
Blood Bilirubin IncreasedInvestigations
HeadachesNervous system disorders
VomitingGastrointestinal disorders
Neutrophil Count DecreasedInvestigations
AnorexiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
PainGeneral disorders
DizzinessNervous system disorders
ProteinuriaRenal and urinary disorders
Blurred VisionEye disorders
NauseaGastrointestinal disorders
SinusitisInfections and infestations
Urinary Tract InfectionInfections and infestations
FallInjury, poisoning and procedural complications
AmnesiaNervous system disorders
DysphasiaNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HoarsenessRespiratory, thoracic and mediastinal disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
TinnitusEar and labyrinth disorders
Edema LimbsGeneral disorders
FeverGeneral disorders
Gait DisturbanceGeneral disorders

Most-reported serious reactions: Disease Progression, Seizure, Clinical Decline, Headache, Febrile Neutropenia, Viral Gastroenteritis, Pleural Effusion, Transient Ischemic Attack.

Data from ClinicalTrials.gov NCT01898130 adverse events section.

Sponsor's own description

This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease has spread to their brain. This study will not evaluate the effect of bevacizumab on the systemic solid tumor cancer. Bevacizumab is a medication and it is thought that bevacizumab may interfere with the growth of new blood vessels; therefore it might stop tumor growth and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels.

Publications & conference data

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

  1. Treatment of Brain Metastases.
    Lin X, DeAngelis LM. · · 2015 · cited 295× · PMID 26282648 · DOI 10.1200/jco.2015.60.9503
  2. Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy.
    Vacchelli E, Aranda F, Eggermont A, Galon J, et al · · 2014 · cited 54× · PMID 24605265 · DOI 10.4161/onci.27048
  3. Targeted therapies in brain metastases.
    Lin NU. · · 2014 · cited 38× · PMID 24353011 · DOI 10.1007/s11940-013-0276-z
  4. Developmental therapeutics for patients with breast cancer and central nervous system metastasis: current landscape and future perspectives.
    Costa R, Carneiro BA, Wainwright DA, Santa-Maria CA, et al · · 2017 · cited 33× · PMID 28177431 · DOI 10.1093/annonc/mdw532
  5. Clinicopathologic characteristics and survival of patients with gynecologic malignancies metastatic to the brain.
    Divine LM, Kizer NT, Hagemann AR, Pittman ME, et al · · 2016 · cited 25× · PMID 27117923 · DOI 10.1016/j.ygyno.2016.04.030
  6. TAMs in Brain Metastasis: Molecular Signatures in Mouse and Man.
    Schulz M, Sevenich L. · · 2021 · cited 12× · PMID 34539650 · DOI 10.3389/fimmu.2021.716504
  7. Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.
    Kotecha R, La Rosa A, Brown PD, Vogelbaum MA, et al · · 2025 · cited 6× · PMID 39495010 · DOI 10.1093/neuonc/noae220
  8. Mechanisms, Imaging Phenotypes, and Therapeutic Advances of Neovascularization in Brain Metastases.
    Liu S, Shan B, Zhang Y, Xu L, et al · · 2026 · PMID 41595655 · DOI 10.3390/biomedicines14010119

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