Phase I Trial Combining Sulfasalazine and Gamma Knife Radiosurgery for Recurrent Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Toxicity (Common Terminology Criteria for Adverse Event v 4.0)
研究概览
简要总结
This study evaluates the safety associated with the addition of sulfasalazine to stereotactic radiosurgery for recurrent glioblastoma. Sulfasalazine is a potential tumor selective radiosensitizer.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically verified glioblastoma multiforme with recurrence (first or second relapse, all subtypes) based on the Response Assessment in Neuro-Oncology criteria.
- •Prior standard therapy for newly diagnosed glioblastoma consisting of surgery, standard fractionated radiotherapy to 60 Gy concomitant with Temozolomide
- •Has been informed of other treatment options
- •Must be eligible to gamma knife treatment
- •Tumor size ≤ 3 cm in diameter (≤ 15 cm3 ) on MRI dated no more than 30 days before SRS treatment
- •Must be at least 18 years of age
- •Must be ambulatory with a Karnofsky performance status of ≥ 70
- •Life expectancy > 12 weeks
- •Laboratory parameters for vital functions should be in the normal reference range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified:
- •Hematology: White blood cell count: ≥ 3.0 x 109/l, Platelet count:: ≥ 100 x 109/l, Hemoglobin: ≥ 100 g/l, Total bilirubin level: <1.5 times the upper limit of normal (ULN) (except in patients with Gilbert's Syndrome who must have a total bilirubin less than 51,3 µmol/L), alanine aminotransferase < 3 times the ULN, Creatinine < 1.5 times the ULN, Normal prothrombin time / international normalized ratio (PT INR) < 1.4, Absolute neutrophil count: ≥ 1 x109/L without the support of filgrastim.
- •More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
- •Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to national/local regulations
排除标准
- •Allergy to sulfa drugs
- •Adverse reactions to salicylates
- •Known hypersensitivity to sulfasalazine, its metabolites or any of the excipients (Povidone; Maize starch; magnesium stearate; colloidal silicon dioxide)
- •Eligible to alternative standard treatments with temozolomide
- •Treatment with sulfasalazine after glioblastoma diagnosis
- •Participation in pharmacokinetic trial within 4 weeks
- •Participation in immunotherapy trial within 4 weeks
- •History of psychological symptoms affecting ability to consent to and/or fulfill the protocol
- •Other malignant diseases and multiple sclerosis
- •Pregnant or breast feeding patients.
- •Porphyria
- •Kidney of liver deficiencies
- •Glucose-6-phosphate dehydrogenase deficiency
- •Severe allergy or bronchial asthma
- •History of erythema multiforme
- •Significant heart failure or renal failure
- •Intestinal or urinary obstruction
- •Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures).
研究组 & 干预措施
Sulfasalazine in addition to stereotactic radiosurgery
3 + 3 dose escalation The first cohort of 3-6 patients will receive 1.5 g Sulfasalazine daily for 3 days before single fraction stereotactic radiosurgery utilizing 12 Gy prescription dose to the tumor margin.
The second, third and fourth cohort will receive 3 days pretreatment with 3 g, 4.5 g and 6 g Sulfasalazine, respectively, before 12 Gy single fraction stereotactic radiosurgery.
干预措施: Sulfasalazine (Drug)
结局指标
主要结局
Toxicity (Common Terminology Criteria for Adverse Event v 4.0)
时间窗: 1 month
Determining the maximum tolerated and recommended dose of sulfasalazine as radiosensitizer.
次要结局
- Progression free survival(1 year)
- Overall survival(2 years)
- Quality of life (Functional Assessment of Cancer Therapy-Brain)(1 year)
- Presence of radiation necrosis(1 month)
- Intratumoral Glutathione production(4 days)
- Karnofsky performance score (KPS)(1 year)
- Steroid use in mg over time(1 year)