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Trial record 2 of 22 for:    radiosurgery | Glioblastoma Multiforme

Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT02120287
Recruitment Status : Active, not recruiting
First Posted : April 22, 2014
Last Update Posted : May 21, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Ajay Niranjan, University of Pittsburgh

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Glioblastoma - Category Drug: Bevacizumab Procedure: Magnetic Resonance Spectroscopy (MRS) Procedure: Border Zone Stereotactic Radiosurgery (BZ-SRS) Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Phase II Study of Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Multiforme
Study Start Date : May 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
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

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.
Other Name: Avastin

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.
Other Name: GammaKnife




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Two years ]
    To assess the efficacy of Border Zone SRS with bevacizumab by overall survival in patients with recurrent or progressive glioblastoma following conventional management with surgery, fractionated radiation therapy, and chemotherapy.


Secondary Outcome Measures :
  1. Survival at 6 months [ Time Frame: Six months ]
    To estimate progression-free and overall survival at 6 months

  2. CNS Toxicity [ Time Frame: Six months after SRS ]
    To evaluate the CNS late toxicity of combined treatment

  3. Survival compared to historical outcome [ Time Frame: Two years ]
    To evaluate survival following border zone SRS with bevacizumab in comparison to historical outcome

  4. Tumor Response & Radiosurgical Toxicity [ Time Frame: Two years ]
    To evaluate whether border zone SRS with bevacizumab improves tumor response or reduces radiosurgical toxicity compared to historical outcomes

  5. Quality of Life [ Time Frame: Two years ]
    To evaluate the quality of life of border zone SRS with bevacizumab administration

  6. Magnetic Resonance Spectroscopy (MRS) [ Time Frame: Two years ]
    To evaluate the potential value of magnetic resonance spectroscopy (MRS) in improvement of border zone target selection and detection of therapeutic response



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120287


Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Ajay Niranjan
Genentech, Inc.
Investigators
Principal Investigator: Ajay Niranjan, MD University of Pittsburgh

Responsible Party: Ajay Niranjan, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02120287     History of Changes
Other Study ID Numbers: 13-063
First Posted: April 22, 2014    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ajay Niranjan, University of Pittsburgh:
Border Zone Stereotactic Radiosurgery
Bevacizumab
Recurrent Glioblastoma Multiforme
Progressive Glioblastoma Multiforme
Magnetic Resonance Spectroscopy
Glioblastoma
Brain Cancer
Brain Tumor
Radiosurgery

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents