This study evaluates the safety associated with the addition of sulfasalazine to stereotactic radiosurgery for recurrent glioblastoma. Sulfasalazine is a potential tumor selective radiosensitizer.
Glioblastoma is the most aggressive and most common type of primary brain cancer. Standard treatment at diagnosis is surgery followed by high dose radiation therapy and chemotherapy. Despite initial treatment nearly all patients will experience recurrence of the tumor with a dismal prognosis. There is no consensus on standard of care at recurrence. Reoperation is associated with a high risk of complications and further conventional radiation therapy is often not possible as the maximum tolerated dose to the normal brain has already been given. In addition most tumors have developed resistance towards chemotherapy. Stereotactic radiosurgery (SRS) may be administered despite prior initial radiation treatment but in order to avoid radiation induced complications only limited doses to limited tumor volumes can be applied. Developing new strategies to improve the effect of radiation selectively on tumor cells without simultaneously increase the radiation induced damage of normal brain would be valuable. The investigators have shown in experimental studies that the drug sulfasalazine enhances the number of cancer cells that dies as result of radiation therapy and thereby improves survival in combination with SRS in animals with glioblastoma. Sulfasalazine inhibits the production of an antioxidant that normally protects the tumor against radiation. Hopefully the trial will result in a new and more effective treatment option for patients with recurrent glioblastoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Sulfasalazine combined with stereotactic radiosurgery
Haukeland University Hospital
Bergen, Norway
Toxicity (Common Terminology Criteria for Adverse Event v 4.0)
Determining the maximum tolerated and recommended dose of sulfasalazine as radiosensitizer.
Time frame: 1 month
Intratumoral Glutathione production
Monitor the effect of sulfasalazine on the level of Glutathione production in glioma cells.
Time frame: 4 days
Presence of radiation necrosis
Monitor late toxicity of sulfasalazine combined with stereotactic radiosurgery on Positron Emission Tomography.
Time frame: 1 month
Progression free survival
Monitor the preliminary effect of sulfasalazine combined with stereotactic radiosurgery on local tumor control.
Time frame: 1 year
Overall survival
Assess the preliminary efficacy of sulfasalazine in combination with SRS on survival.
Time frame: 2 years
Quality of life (Functional Assessment of Cancer Therapy-Brain)
Assess the preliminary efficacy of sulfasalazine in combination with SRS on changes in quality of life utilizing the brain cancer subscale of the functional assessment of cancer therapy-Brain (FACT-Br) questionaire. The brain cancer subscale consists of twenty-three items regarding neurological concerns (range: 0-76 points). The response to the items uses a five-point scale ranging from 0 (not at all) to 4 (very much). The higher the patient score, the better the quality of life.
Time frame: 1 year
Karnofsky performance score (KPS)
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Assess the preliminary efficacy of sulfasalazine in combination with stereotactic radiosurgery on changes in the Karnofsky performance score (range 0 - 100 points). The higher the score, the better is the functional performance status of the patient.
Time frame: 1 year
Steroid use in mg over time
Assess the preliminary efficacy of sulfasalazine in combination with stereotactic radiosurgery on the patients´ need for steroid medication. The change in steroid use in mg from baseline up to 1 year following radiosurgery will be evaluated using descriptive statistics.
Time frame: 1 year