Clinical trial · Interventional
Sulfasalazine and Stereotactic Radiosurgery for Recurrent Glioblastoma
Phase I Trial Combining Sulfasalazine and Gamma Knife Radiosurgery for Recurrent Glioblastoma
NCT04205357CI-TRIAL-00064414SAS-GKRScompletedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study evaluates the safety associated with the addition of sulfasalazine to stereotactic radiosurgery for recurrent glioblastoma. Sulfasalazine is a potential tumor selective radiosensitizer.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
| Glioma | Glioma | ONTOLOGY_EXACT | 0.98 |
| Recurrent Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Sulfasalazine | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- OTHER
- label
- Sulfasalazine in addition to stereotactic radiosurgery
- description
- 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.
- interventionNames
- Drug: Sulfasalazine
Primary outcomes (1)
- measure
- Toxicity (Common Terminology Criteria for Adverse Event v 4.0)
- timeFrame
- 1 month
- description
- Determining the maximum tolerated and recommended dose of sulfasalazine as radiosensitizer.
Secondary outcomes (7)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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 Exclusion Criteria: * 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).
References
Publications (11)
- BACKGROUNDSleire L, Skeie BS, Netland IA, Forde HE, Dodoo E, Selheim F, Leiss L, Heggdal JI, Pedersen PH, Wang J, Enger PO. Drug repurposing: sulfasalazine sensitizes gliomas to gamma knife radiosurgery by blocking cystine uptake through system Xc-, leading to glutathione depletion. Oncogene. 2015 Dec 3;34(49):5951-9. doi: 10.1038/onc.2015.60. Epub 2015 Mar 23. PMID 25798841
- BACKGROUNDSkeie BS, Enger PO, Brogger J, Ganz JC, Thorsen F, Heggdal JI, Pedersen PH. gamma knife surgery versus reoperation for recurrent glioblastoma multiforme. World Neurosurg. 2012 Dec;78(6):658-69. doi: 10.1016/j.wneu.2012.03.024. Epub 2012 Apr 4. PMID 22484078
- BACKGROUNDDodoo E, Huffmann B, Peredo I, Grinaker H, Sinclair G, Machinis T, Enger PO, Skeie BS, Pedersen PH, Ohlsson M, Orrego A, Kraepelien T, Barsoum P, Benmakhlouf H, Herrman L, Svensson M, Lippitz B. Increased survival using delayed gamma knife radiosurgery for recurrent high-grade glioma: a feasibility study. World Neurosurg. 2014 Nov;82(5):e623-32. doi: 10.1016/j.wneu.2014.06.011. Epub 2014 Jun 13. PMID 24930898
- BACKGROUNDSontheimer H, Bridges RJ. Sulfasalazine for brain cancer fits. Expert Opin Investig Drugs. 2012 May;21(5):575-8. doi: 10.1517/13543784.2012.670634. Epub 2012 Mar 12. PMID 22404218
- BACKGROUNDChung WJ, Lyons SA, Nelson GM, Hamza H, Gladson CL, Gillespie GY, Sontheimer H. Inhibition of cystine uptake disrupts the growth of primary brain tumors. J Neurosci. 2005 Aug 3;25(31):7101-10. doi: 10.1523/JNEUROSCI.5258-04.2005. PMID 16079392
- BACKGROUNDSkeie BS, Wang J, Dodoo E, Heggdal JI, Gronli J, Sleire L, Bragstad S, Ganz JC, Chekenya M, Mork S, Pedersen PH, Enger PO. Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a human GBM xenograft model. Biomed Res Int. 2013;2013:139674. doi: 10.1155/2013/139674. Epub 2013 Nov 10. PMID 24312904