Clinical trial NCT02085304: Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM
Official title: Phase I/II Randomized Prospective Trial for Newly Diagnosed GBM, With Upfront Gross Total Resection, Gliadel®, Followed by Temodar® With Concurrent IMRT Versus GK
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Keywords: Glioblastoma
GBM
Radiation
GammaKnife(R)
Radiosurgery
Gliadel(R)
Temozolomide
Temodar(R)
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2014-03-12
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in health related quality of life
timeFrame: Every two months from baseline, postoperatively before start of radiation/GK up to 24 months
measure: time without Cognitive impairment
timeFrame: Time to event assessed every four months from baseline up to 24 months
Secondary outcomes:
measure: incidence of symptomatic radiation necrosis
timeFrame: time from RT/GK assessed every two months up to 24 months
measure: Disease-free survival
timeFrame: Time from date of study enrollment until the date of first documented disease recurrence assessed up to 100 months
measure: Overall survival
timeFrame: time from date of study enrollment to date of death assessed up to 100 months
Other outcomes:
measure: Utility of perfusion MRI imaging
timeFrame: time from baseline assessd up to 24 months
measure: Determine predictive value of gammaknife cell culture bioassay
timeFrame: baseline and at recurrence assessed up to 100 months
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
state: Arizona
Study officials:
affiliation: Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
name: Kris A Smith, MD
role: STUDY_CHAIR
References: