A phase I study of Iobenguane I 131 to evaluate MTD, efficacy and safety in patients with malignant pheochromocytoma/paraganglioma (Pheo).
4605 Background: I-131-iobenguane, a substrate for the norepinephrine transporter, has been shown to be effective in the treatment of neuroendocrine cancers such as Pheo. Non-radioactive iobenguane has been shown to inhibit uptake of radioiodinated iobenguane by tumors and has potential to cause cardiovascular AEs. Ultratrace Iobenguane I 131 (Ultratrace) is prepared so that the final drug product is devoid of cold iobenguane thereby enhancing tumor accumulation and limiting dose dependent AEs. METHODS: Patients with metastatic/recurrent Pheo with >1 CT-measurable lesion scintigraphically visualized with Ultratrace were enrolled. Ultratrace dose escalation used a 3+3 modified Fibonacci design; initiated at 6.0 mCi/kg and escalated in 1.0 mCi/kg increments. Safety and efficacy data were obtained including tumor measurements by CT/MRI volume, RECIST criteria and tumor markers. RESULTS: 15 patients enrolled in the dose escalation study. Data were available for analysis on 9 patients (mean age: 51 yrs; 4 males) from 3 dose groups (6, 7 and 8 mCi/kg up to a max. of 75 kg body weight). The median weight was 84.2 kg (range: 42, 126). Total administered dose ranges for each dose cohort were 333 to 428 mCi, 325 to 536 mCi, and 473 to 601 mCi, respectively. No protocol defined DLTs were observed at the 6 or 7 mCi/kg dose levels. One patient at the 8 mCi/kg dose experienced grade 4 thrombocytopenia, and no intervention was required. No CV effects were observed. At 3- and 6-month follow up, CT/MRI scans were available for 5 and 2 patients, respectively. All patients showed decreases in the longest diameter per RECIST (-15%, -18%, -6%, -10%, -10%; -15%, -24%), and 4 and 2 patients with available data showed decreases or stabilization in tumor volume (-28%, -25%, 0%, -17%; -29% and -46%). Also, all 5 patients showed a decline in serum chromogranin A levels (range: -22% to -75%) and other tumor markers, and ∼50% showed improvements in HTN and tumor pain. CONCLUSIONS: Reductions in tumor volume, tumor dimension per RECIST, and tumor markers were observed in all 5 evaluable patients at 3 months after a single Ultratrace dose. Improvements in HTN and pain occurred in ∼50%. Dose escalation is proceeding. [Table: see text].
Morse, MA; Babich, JW; LaFrance, N; Kacena, KA; Gockerman, J; Moore, J; Coleman, RE
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