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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02085304
Recruitment Status : Unknown
Verified December 2016 by St. Joseph's Hospital and Medical Center, Phoenix.
Recruitment status was:  Recruiting
First Posted : March 12, 2014
Last Update Posted : December 13, 2016
Sponsor:
Information provided by (Responsible Party):
St. Joseph's Hospital and Medical Center, Phoenix

Tracking Information
First Submitted Date  ICMJE March 7, 2014
First Posted Date  ICMJE March 12, 2014
Last Update Posted Date December 13, 2016
Study Start Date  ICMJE October 2012
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2014)
  • Change in health related quality of life [ Time Frame: Every two months from baseline, postoperatively before start of radiation/GK up to 24 months ]
    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.
  • time without Cognitive impairment [ Time Frame: Time to event assessed every four months from baseline up to 24 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02085304 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2014)
  • incidence of symptomatic radiation necrosis [ Time Frame: time from RT/GK assessed every two months up to 24 months ]
  • Disease-free survival [ Time Frame: Time from date of study enrollment until the date of first documented disease recurrence assessed up to 100 months ]
  • Overall survival [ Time Frame: time from date of study enrollment to date of death assessed up to 100 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 10, 2014)
  • Utility of perfusion MRI imaging [ Time Frame: time from baseline assessd up to 24 months ]
    Utility of perfusion MRI imaging for detection and differentiation between radiation toxicity and tumor recurrence
  • Determine predictive value of gammaknife cell culture bioassay [ Time Frame: baseline and at recurrence assessed up to 100 months ]
    A new gamma knife cell culture bioassay developed at our center will be utilized to determine if it has a predictive value of responsiveness to radiosurgery in the clinical setting.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM
Official Title  ICMJE Phase I/II Randomized Prospective Trial for Newly Diagnosed GBM, With Upfront Gross Total Resection, Gliadel®, Followed by Temodar® With Concurrent IMRT Versus GK
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.
Detailed Description

The primary purpose of this study is to determine if single fraction GK radiosurgical treatment to the resection bed can achieve equivalent local control and survival for patients with GBM after GTR, Gliadel® implant and temozolomide therapy compared to patients receiving standard postoperative RT with temozolomide, but offer improved quality of life and preserve cognitive function.

In Phase I, it is proposed that 20 patients with newly diagnosed glioblastoma multiforme (GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to the resection cavity at that time will be eligible for study. These patients will then receive Gamma Knife® (GK) radiosurgery to the resection cavity margin within 4 weeks following surgical resection and within 24 hours of starting temozolomide (Temodar®) induction therapy. Temozolomide (Temodar®) maintenance therapy would be administered for 12 months.

In Phase II, it is proposed that 60 patients with newly diagnosed glioblastoma multiforme (GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to the resection cavity at the time of initial resection will be eligible for study. These patients will then be randomized to either standard fractionated conformal radiation therapy (RT) or Gamma Knife® (GK) radiosurgery to the resection cavity margin. Fractionated RT would be administered with concurrent temozolomide Gamma knife® radiosurgery to the resection cavity margin will be administered within 24 hours of starting temozolomide induction therapy. Both the GK and RT will be administered within 4 weeks following surgical resection. Temozolomide (Temodar®) maintenance therapy would be administered to all patients in both arms of the study for 12 months.

It is believed that all patients will benefit from enrollment in the study regardless of the treatment arm to which they are randomized. All patients will be receiving focally aggressive surgical resection with Gliadel® implant in addition to temozolomide for prevention of both focal and distant recurrence.

Patients who are randomized to receive GK radiosurgical treatment to the resection bed margin may benefit from increased local control based on a prior non-randomized study. However these patients will be treated in a non-standard fashion and may be subjected to a higher incidence of focal radiation necrosis or a higher incidence of failure beyond the resection margin compared to standard patients.

The GK treated patients however, will be spared the standard 6 weeks of RT postoperatively. It is hypothesized that those receiving GK will therefore have an improved quality of life with respect to having less fatigue, lack of hair loss and a decreased incidence of delayed cognitive decline associated with standard RT.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Procedure: Gross total resection and Gliadel(R) wafers implanted
    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.
  • Radiation: GammaKnife(R) stereotactic Radiosurgery
    GammaKnife® (GK) radiosurgery dose of 15 Gy in one fraction to the resection cavity margin
  • Radiation: Standard fractionated radiation therapy
    standard fractionated RT of 60 Gy in 30 fractions (over approximately six weeks)
  • Drug: Temozolomide
    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.
    Other Name: Temodar(R)
Study Arms  ICMJE
  • Experimental: GammaKnife(R) stereotactic radiosurgery
    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.
    Interventions:
    • Procedure: Gross total resection and Gliadel(R) wafers implanted
    • Radiation: GammaKnife(R) stereotactic Radiosurgery
    • Drug: Temozolomide
  • Active Comparator: Standard fractionated radiation therapy
    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.
    Interventions:
    • Procedure: Gross total resection and Gliadel(R) wafers implanted
    • Radiation: Standard fractionated radiation therapy
    • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 10, 2014)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02085304
Other Study ID Numbers  ICMJE 12BN101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Joseph's Hospital and Medical Center, Phoenix
Study Sponsor  ICMJE St. Joseph's Hospital and Medical Center, Phoenix
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Kris A Smith, MD Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
PRS Account St. Joseph's Hospital and Medical Center, Phoenix
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP