Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

All patients will receive Border Zone Stereotactic Radiosurgery (BZ-SRS) and additionally receive bevacizumab (10 mg/kg) one day before and then at day 14 followed by 10 mg/kg/day every 14 days until progression.

One to 14 days before BZ- SRS procedure, patients at centers with MRS experience will undergo standard brain MRI /MRS

Patients will receive bevacizumab (10 mg/kg) one day before and then at day 14 followed by10 mg/kg/day every 14 days until progression.

Magnetic Resonance Spectroscopy (MRS)

The 'border zone' of the tumor will be targeted by SRS in a single session.

Border Zone Stereotactic Radiosurgery (BZ-SRS)

Ajay Niranjan, MD

This is a phase II study on the usage of stereotactic Gamma Knife radiosurgery as a boost to the tumor bed border zone in conjunction with the usage of bevacizumab.

Glioblastoma Multiforme (GBM) is the most common primary brain tumor in adults. Unfortunately, despite aggressive surgery, radiation therapy (RT) and chemotherapy, the prognosis for this disease is poor. It is our hypothesis that GBM is a "local" disease wherein treatment failure is due to failure to eradicate tumor cells in the pathways along which the tumor eventually spreads (the "border zone").

The investigators hypothesize that treatment volume escalation will be successful at improving overall survival in patients with GBM when appropriate targeting and precision dose delivery is performed in a single treatment session. The 'border zone' of the tumor will be targeted for SRS (defined as a combination of the MRI volume of gadolinium enhancement plus up to 2 cm of the surrounding T2 volume). This represents the volume of tumor infiltrated white matter and is the route of GBM spread. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), has been used with safety and clinical success with concomitant chemotherapy in solid tumors, including GBM.

The investigators further hypothesize that a combined approach of SRS with this VEGF inhibitor will be an effective strategy for GBM because bevacizumab will maximize the effects of radiation in the treated volume and potentially reduce radiation toxicity in the adjacent brain.

Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme

Multicenter Phase II Study of Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Multiforme

The number of months that a patient remains alive from the day first gamma knife surgery until the date of death or end of data collection for survival.

The proportion of patients who did not experience disease progression per RANO as of 6 months from the date of radiosurgery. RANO (Response Assessment in Neuro-Oncology) Response Criteria for Progression using imaging features: 25% or more increase in enhancing lesions despite stable or increasing steroid dose increase (significant) in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes any new lesions clinical features clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). Proportion of patients for PFS = number of patients without disease at 6 months post radiosurgery / total number of patients.

The proportion of patients who remained alive as of 6 months from the date of radiosurgery. Proportion of patients for OS = number of patients alive at 6 months post radiosurgery / total number of patients.

The number of patients experiencing a CNS toxicity type occurring within 3 months of gamma knife surgery, as measured by RTOG/EORTC Acute Radiation Morbidity Scoring and the NCI CTCAE v4.0 for late toxicity.

Proportion of patients with a best response of CR, PR, SD, PD: number of patients with CR, PR, SD or PD / total number of patients evaluable for response to treatment of border zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab.

Improvement of border zone target selection and detection of therapeutic response of the derived treatment volumes between MRI and MRI+MRS (Magnetic Resonance Spectroscopy).

This is presented as the number of patients for whom the derived treatment was changed as a result of the utilization of MRS.

The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. Score range from 0 to 100; the lower the Karnofsky score, the worse the survival for most serious illnesses. A score of 100 would indicate 'Normal no complaints; no evidence of disease.' A score of 50 indicates 'Requires considerable assistance and frequent medical care.' A score of 0-10 would indicate 'Moribund; fatal processes progressing rapidly' and 'Death'.

The Barthel Index consists items assessing the ability to achieve certain activities without assistance. It evaluates the ability of feeding, moving from wheelchair to bed and returning, doing personal toilet, getting on and off toilet,bathing self, walking on level surface, ascending and descending stairs, dressing, controlling bowels and controlling bladder. Scoring ranged from 0 (completely dependent) to 20 (completely independent) for this assessment. A maximal score of 20 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state.

An assessment comprised of 20 statements for which the participant is asked to indicate how often they have felt a certain way during the past week. SCORING: zero for answers of Rarely or none of the time (less than 1 day), 1 for answers of Some or a little of the time (1-2 days), 2 for answers of Occasionally or a moderate amount of time (3-4 days) the third column, 3 for answers of Most or all of the time (5-7 days). The scoring of positive items is reversed. Possible range of scores is zero to 60, with the higher scores indicating the presence of more depression symptomatology.

The FACT-G is a patient rated, 27-item compilation of general questions divided into 4 primary Quality of Life (QOL) sub-scales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). This tool represents the generic core questionnaire that are utilized in combination with cancer site-specific questionnaires, (FBrain, in this study) Overall score and four subscale scores with ranges and distributions that are sample-specific can be calculated.FACT-G is scored by summing the individual scale scores; higher scores indicate better quality of life. FACT-G uses 5-point rating scale ranging from (0) = Not at all; (1) = A little bit; (2) = Somewhat; (3) = Quite a bit; to (4) = Very much.The FACT-G total score is the sum of the four subscale scores (if least 80% completed) and has a possible range of 0-108 points.

The FACT-BrSI subscale, brain tumor specific version (2007), is a 15-item, patient completed, questionnaire.This brain subscale is used along with the core (general) questionnaire (FACT-G) that includes 27 items. Patients rate all items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher quality of life (QOL). The FACT BrSI has a range of 0-60, where a higher score indicates less symptomatology.

Genentech, Inc.

Ajay Niranjan

Professor

All patients received Border Zone Stereotactic Radiosurgery (BZ-SRS) and additionally received bevacizumab (10 mg/kg) one day before and then at day 14 followed by 10 mg/kg/day every 14 days until disease progression. One to 14 days before BZ- SRS procedure, patients at centers with MRS experience will undergo standard brain MRI /MRS. Patients will have MRS Magnetic Resonance Spectroscopy (MRS)prior to BZ-SRS. Border Zone Stereotactic Radiosurgery (BZ-SRS): The 'border zone' of the tumor will be targeted by SRS in a single session.

BZ-SRS With Bevacizumab

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Patients with recurrent or Progressive Glioblastoma Multiforme who underwent treatment of border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab (10 mg/kg).

Barbara Stadterman

Overall Survival (OS)

Death or disease progression ≤ 6mons of treatment

Alive or stable disease ≥ 6 months of treatment

6-month Progression-free Survival

Death within 6 months of treatment

Alive after 6 months of treatment

6-month Overall Survival

Muscle Weakness Lower Limb

Fatigue and Dehydration

Spinal Fracture and Pain

CNS Toxicity

Complete Response

Partial Response

Stable Disease

Progressed Disease

Tumor Response

Participants who received MRS (Magnetic Resonance Spectroscopy) scans prior to radiosurgery.

Potential Value of Magnetic Resonance Spectroscopy (MRS)

Karnofsky Performance Status Score: 40

Karnofsky Performance Status Score: 60

Karnofsky Performance Status Score: 70

Karnofsky Performance Status Score: 80

Karnofsky Performance Status Score: 90

Karnofsky Performance Status Score: 100

Karnofsky Performance Status

Barthel's Index of Activities of Daily Living Assessment

Center for Epidemiological Studies Depression Scale (CES-D)

Physical Well-Being

Social Well-Being

Emotional Well-Being

Functional Well-Being

Total Well-Being

Patients with recurrent or Progressive Glioblastoma Multiforme who underwent treatment of border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab (10 mg/kg). (NOTE: One participant did not complete the EWB section of the questionnaire. One participant did not complete the FWB section of the questionnaire.)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme	NCT02120287	Glioblastoma Mu... Glioblastoma - ...	Bevacizumab Magnetic Resona... Border Zone Ste...	18 Years -	University of Pittsburgh
Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme	NCT02120287	Glioblastoma Mu... Glioblastoma - ...	Bevacizumab Magnetic Resona... Border Zone Ste...	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for border zone stereotactic radiosurgery