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Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Histologically confirmed glioblastoma multiforme, WHO grade IV astrocytoma. 2. Prior first-line treatment with surgery or biopsy followed by fractionated radiotherapy with concurrent temozolomide-containing chemotherapy is required for glioblastoma patients. Additional prior chemotherapy is allowed, without limitation on number of recurrences. 3. An interval of at least 2 months since completion of fractionated radiotherapy. 4. Age > 18 years. 5. Life expectancy of at least 12 weeks. 6. Karnofsky Performance Status score (KPS) of ≥ 60. 7. Documented recurrent disease; Disease must be evaluable, but does not need to be measurable; the target site for SRS does not need to be located in a previously-irradiated area. 8. All patients must have no restrictions to obtaining MRI with and without gadolinium contrast. 9. Adequate bone marrow, hepatic and renal function ; BUN < 25 and Cr < 1.7. 10. Negative pregnancy test at the time of SRS in any patient who could be pregnant. 11. Willingness to forego additional therapy until evidence of disease progression.

Exclusion Criteria:

1. General Medical Exclusions: 1. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. 2. Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last 3 years. 3. Prior radiosurgery. 4. Prior intracavitary irradiation or Gliadel wafers. 2. Disease-Specific Exclusions: 1. Inability to comply with protocol or study procedures. 2. Prior treatment with bevacizumab. 3. Inability to undergo MRI with and without contrast administration. 3. Bevacizumab-Specific Exclusions: 1. Inadequately controlled hypertension. 2. Prior history of hypertensive crisis or hypertensive encephalopathy. 3. New York Heart Association (NYHA) Grade II or greater congestive heart failure. 4. History of myocardial infarction or unstable angina within 6 months prior to Day 1. 5. History of stroke or transient ischemic attack within 6 months prior to Day 1. 6. Significant vascular disease within 6 months prior to Day 1. 7. History of hemoptysis within 1 month prior to Day 1. 8. Evidence of bleeding diathesis or significant coagulopathy. 9. Major surgical procedure, open biopsy, or significant traumatic injury within 14 days prior to Day 1 or anticipation of need for major non -cranial surgical procedure during the course of the study. 10. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1. 11. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1. 12. Serious, non-healing wound, active ulcer, or untreated bone fracture. 13. Proteinuria. 14. Known hypersensitivity to any component of bevacizumab. 15. Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02120287
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ajay Niranjan
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Ajay Niranjan, MD
Principal Investigator Affiliation University of Pittsburgh Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme, Glioblastoma - Category
Additional Details

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.

Arms & Interventions

Arms

Experimental: BZ-SRS with Bevacizumab

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

Interventions

Drug: - Bevacizumab

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.

Procedure: - Magnetic Resonance Spectroscopy (MRS)

Subjects will have MRS prior to BZ-SRS.

Procedure: - Border Zone Stereotactic Radiosurgery (BZ-SRS)

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Pittsburgh, Pittsburgh, Pennsylvania

Status

Address

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213