Results from a phase I study of 4-l-[131I]iodo-phenylalanine ([131I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1)

Abstract Background Glioblastoma (GBM), the most common malignant brain tumor, is associated with devastating outcomes. IPAX-1 was a multicenter, open-label, single-arm phase I study to evaluate carrier-added 4-L-[131I]iodo-phenylalanine ([131I]IPA) plus external radiation therapy (XRT) in recurrent GBM. Methods A total of 10 adults with recurrent GBM who had received first-line debulking surgery plus radio-chemotherapy, were randomized to a single-dose regimen (1f; 131I-IPA 2 GBq before XRT); a fractionated parallel dose regimen (3f-p; 3 131I-IPA 670 MBq fractions, in parallel with second-line XRT), or a fractionated sequential dose regimen (3f-s; 3 131I-IPA 670 MBq fractions before and after XRT). Metabolic tumor responses were determined using O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography, while single-photon emission computed tomography was used to guide [131I]IPA tumor dosimetry. Results All dose regimens were well tolerated. Organ-absorbed radiation doses in red marrow (0.38 Gy) and kidney (1.28 Gy) confirmed no radiation-based toxicity. Stable disease was observed in 4 of the 9 patients at 3 months post-treatment (3-month follow-up [FU], 1 patient did not reach protocol-mandated end of study), yielding a response rate of 44.4%. At the 3-month FU, 6 patients demonstrated metabolic stable disease. Median progression-free survival was 4.3 months (95% confidence interval [CI]: 3.3–4.5), while median overall survival was 13 months (95% CI: 7.1–27). Conclusions Single or fractionated doses of [131I]IPA plus XRT were associated with acceptable tolerability and specific tumor targeting in patients with recurrent GBM, warranting further investigation. Lay Summary Glioblastoma is a type of brain cancer that is very difficult to treat, especially when it comes back after initial treatments that include surgery, radiation, and chemotherapy. In this study, the authors aimed to see whether a new treatment that combines a radioactive drug called [131I]IPA with radiation therapy could help patients with recurring glioblastoma. To test this, they conducted a small safety trial with 10 patients. The results showed that the treatment did not cause serious side effects at any of the doses they tested. Additionally, 4 patients did not see their tumors grow for 3 months after treatment. On average, patients lived for 13 months after receiving this tested treatment.