(AS2) Phase I Trial of Sulfasalazine Combined with Stereotactic Radiosurgery for Recurrent Glioblastoma: Study Protocol and Preliminary Results for NCT04205357

Introduction: Glioblastoma (GBM) is an aggressive, radioresistant type of cancer with a dismal prognosis. Preclinically, Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties by blocking the uptake of cysteine through the xCT-channel, a rate-limiting step for the high intratumoral production of the antioxidant glutathione (GSH). We examined the safety and therapeutic potential of Salazopyrin in combination with Gamma Knife Radiosurgery (GKRS) in patients with recurrent glioblastoma. The trial was funded by the Norwegian Cancer Society.

Methods: We conducted a phase 1 trial of Salazopyrin, which used a 3+3 design with four dose cohorts (1.5, 3.0, 4.5 or 6.0 g/day) with 11C-MET PET/MRI confirmed recurrent GBM following STUPP protocol at diagnosis. Patients underwent GKRS with 12Gy prescription dose following 3 days of pretreatment with SAS. Primary end-point was to establish the recommended dose for efficacy testing in phase II/III trials. Secondary end-points included assessment of progression-free survival (PFS) compared to historical controls.

Results: Between May 5, 2020 and September 2, 2022, 12 patients with recurrent GBM were recruited and included in the analysis.
The preliminary results showed that treatment was safe. No dose-limiting toxicity was reached. The median progression free survival was 12.1 months (95 % CI 3.5 – 20.5) compared to 1.8 (95 % CI 0.3 -3.3) for historical controls, p = 0.008.

Conclusion : Salazopyrin with radiation had acceptable adverse event profile with preliminary evidence of response in patients with recurrent GBM. We are planning a higher phase multicenter trial with a larger cohort of patients powered to investigate PFS.