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

Abstract Purpose: 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 ([ 131 I]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 radiochemotherapy, were randomized to a single dose regimen (1f; 131 I-IPA 2 GBq before XRT); a fractionated parallel dose regimen (3f-p; three 131 I-IPA 670 MBq fractions, in parallel with second-line XRT), or a fractionated sequential dose regimen (3f-s; three 131 I-IPA 670 MBq fractions before and after XRT). Metabolic tumor responses were determined using O-(2- [ 18 F]fluoroethyl)-L-tyrosine positron emission tomography, while single-photon emission computed tomography was used to guide [ 131 I]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 9 patients at 3-month (mo) post-treatment (3-mo follow-up [FU], 1 patient did not reach protocol-mandated end of study), yielding a response rate of 44.4%. At the 3-mo FU, 6 patients demonstrated metabolic stable disease. Median progression-free survival was 4.3 months (95% confidence interval, 3.3–4.5), while median overall survival was 13 months (95% confidence interval, 7.1–27). Conclusion: Single or fractionated doses of [ 131 I]IPA plus XRT were associated with acceptable tolerability and specific tumor targeting in patients with recurrent GBM, warranting further investigation.