Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM

NCT02085304 | Terminated Phase 1 DMC

• 1 other identifier: 12BN101
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

A glioblastoma (GBM) is the most common malignant primary brain tumor, yet it is not easy to control. Recent studies show that survival improves for patients who get aggressive surgery to remove a tumor before starting radiation (RT) and chemotherapy (chemo) treatment. Surgery, RT and chemo are part of regular cancer care for GBM. RT is usually done in daily doses 5 days a week over about 6 weeks. Beams of radiation are aimed at the tumor site plus some of the normal brain tissue around the tumor area. GammaKnife® (GK) radiosurgery also delivers radiation but in a larger dose over one day. GK sends beams to a precise target (tumor location) and very little normal brain tissue that is nearby. This study will compare GK treatment to the usual RT treatment after surgery, and with chemo. We want to know:

• How well each treatment keeps the tumor from growing back.
• What the effects (good and bad) of the treatments are.
• How you rate your quality of life.
• How the treatment affects your ability to think, understand, reason, and remember.
• How you rate your ability to think, understand, reason, and remember.
• If using a certain type of MRI scan can show the difference between new tumor growth and changes caused by treatment.
• If certain features found in tumor cells can help doctors predict how tumors will respond to treatment.

Conditions

Glioblastoma

Keywords

Glioblastoma; GBM; Radiation; GammaKnife(R); Radiosurgery; Gliadel(R); Temozolomide; Temodar(R)

Outcome Measures

Primary Outcomes (2)

• Change in health related quality of life

  health related quality of life (HRQOL) evaluations using the EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QLQ C30/BCM20) and the The Functional Assessment of Cancer Therapy-Brain (FACT-Br, version 4) and cognition, (FACT-Cog, version 3) questionnaires.

  Every two months from baseline, postoperatively before start of radiation/GK up to 24 months

• time without Cognitive impairment

  Intellectual functioning, processing speed, attention and concentration, language and verbal fluency and motor skill as well as mood, depression, and memory assessments will be done prior to RT/GK treatment and at 4 month intervals. A self-report of perceived cognition, will also be completed by patient. Therefore, there will be both an objective measurement of cognition and subjective measurement as a part of quality of life.

  Time to event assessed every four months from baseline up to 24 months

Secondary Outcomes (3)

• incidence of symptomatic radiation necrosis

  time from RT/GK assessed every two months up to 24 months

• Disease-free survival

  Time from date of study enrollment until the date of first documented disease recurrence assessed up to 100 months

• Overall survival

  time from date of study enrollment to date of death assessed up to 100 months

Other Outcomes (2)

• Utility of perfusion MRI imaging

  time from baseline assessd up to 24 months

• Determine predictive value of gammaknife cell culture bioassay

  baseline and at recurrence assessed up to 100 months

Study Arms (2)

GammaKnife(R) stereotactic radiosurgery

EXPERIMENTAL

Following surgery for Gross total resection and Gliadel(R) wafers implanted , the patient will receive a one-day GammaKnife(R) stereotactic radiosurgery procedure and will also take temozolomide (Temodar(R)) chemotherapy daily for six weeks with a one month break before taking temodar for additional 12 monthly cycles.

Procedure: Gross total resection and Gliadel(R) wafers implanted; Radiation: GammaKnife(R) stereotactic Radiosurgery; Drug: Temozolomide

Standard fractionated radiation therapy

ACTIVE COMPARATOR

Following surgery for Gross total resection and Gliadel(R) wafers implanted , the patient will receive six weeks of standard fractionated radiation therapy plus daily temozolomide (Temodar(R)) chemotherapy for six weeks. This is followed by a one month break before taking temodar for additional 12 monthly cycles.

Procedure: Gross total resection and Gliadel(R) wafers implanted; Radiation: Standard fractionated radiation therapy; Drug: Temozolomide

Interventions

Gross total resection and Gliadel(R) wafers implanted PROCEDURE

Complete removal of tumor and implant of Gliadel(R) wafers that are small, dime-sized wafers designed to deliver the chemo drug, carmustine, directly into the cavity made when the brain tumor was removed.

GammaKnife(R) stereotactic radiosurgery; Standard fractionated radiation therapy

GammaKnife(R) stereotactic Radiosurgery RADIATION

GammaKnife® (GK) radiosurgery dose of 15 Gy in one fraction to the resection cavity margin

GammaKnife(R) stereotactic radiosurgery

Standard fractionated radiation therapy RADIATION

standard fractionated RT of 60 Gy in 30 fractions (over approximately six weeks)

Standard fractionated radiation therapy

Temozolomide DRUG

temozolomide 75 mg/m2 daily for 42 days, will be administered to all patients beginning within 24 hours of GK/RT initiation as is routine clinical care. There will be a one month drug holiday following the 42 days before adjuvant chemotherapy begins. Adjuvant temozolomide administered 5 days monthly at 150-200 mg/m2/day will be administered for 12 months as is routine clinical care.

Also known as: Temodar(R)

GammaKnife(R) stereotactic radiosurgery; Standard fractionated radiation therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• single enhancing lesion of the brain with MRI appearance consistent with GBM
• Must be appropriate for Gliadel® wafer implant
• Pathologic confirmation of GBM
• no gross residual tumor found on the immediate postoperative MRI scan
• Volumetric measurements of the resection cavity margin being \< 50 cc
• Karnofsky performance status (KPS) 80% or better
• Must be able to undergo MRI imaging with gadolinium
• Willingness to have follow up visits at Barrow Neurological Institute(BNI)

You may not qualify if:

• multi-focal tumors
• tumors which extend across the corpus callosum,
• residual nodular disease
• Tumors, with a contraindication to Gliadel® implant, such as an anticipated extensive ventricular opening resulting from complete resection.
• Tumor measuring greater than 50cc in volume (on post-operative scan) Volume \< 50 cc if volume if a significant volume of eloquent tissue is included in the proposed treatment volume
• Unable to undergo MRI with gadolinium
• History of cancer within 2 years of GBM diagnosis (basal and squamous cell skin cancers are allowed)
• Patient is not willing to follow up at BNI

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead

Study Sites (1)

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiosurgery; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kris A Smith, MD

  Barrow Neurological Institute at St. Joseph's Hospital and Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 12, 2014
• Study Start: May 7, 2013
• Primary Completion: May 30, 2015
• Study Completion: May 29, 2018
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

US (1)