Penn Clinical Trials: Azedra Trial in Rare Neuroendocrine Tumors (Phase 2b)

Daniel A. Pryma, MD

Earlier this month, Penn Medicine’s Daniel A. Pryma, MD, shared the findings of the pivotal Phase 2b trial of AZEDRA® (iobenguane I131) at the American Society of Clinical Oncology’s ASCO 2018 annual meeting

A targeted radiotherapy agent, Azedra was developed to treat patients with malignant, recurrent, or nonresectable pheochromocytoma and paraganglioma (pheo/para). 

Dr. Pryma, Division Chief, Nuclear Medicine and Clinical Molecular Imaging at Penn Medicine, was the principal investigator for this study, A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma, which is the largest prospective clinical trial in pheo/para to date.

What are Paragangliomas and Pheochromocytomas? (Pheo/Para)

Paragangliomas are rare functional neuroendocrine tumors that are categorized as pheochromocytomas when arising from the adrenal gland. Through the release of hormones, these cancers may provoke severe, resistant and potentially lethal hypertension and arrhythmias. 

Advanced pheo/para is currently incurable. Treatments include surgery, radiotherapy, chemotherapy, targeted therapies and medications for symptomatic control.

Evaluating AZEDRA®

The primary endpoint of the Azedra trial was sustained reduction (including discontinuation) of all antihypertensive medication by at least 50%, with secondary outcome measures including proportion of subjects with complete or partial tumor response by RECIST criteria and overall survival. 

Scan of a large extra-adrenal pheochromocytoma“This is an unusual primary endpoint for a cancer trial,” Dr. Pryma explained. “Because the disease is rare, a standard randomized trial looking for a survival benefit is notpractically feasible, Since hypertension in pheo/para causes significant consequences — including death in up to 30% of patients — controlling it would be evidence of a positive effect of the treatment,” he continued. 

In patients with pheo/para, control of hypertension, as manifested by a consistent reduction in the need for antihypertensive medication, is associated with clinical benefit and improved quality of life.

"Furthermore, in pheo/para patients, the primary cause of death is tumor progression,” Dr. Pryma explained in a recent interview. “In this study, 98% of patients who received two doses experienced stable disease or better as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Moreover, the patients treated with Azedra were able to achieve control of catecholamine-associated hypertension.”

A meaningful proportion of patients treated in the study (25%) achieved sustained reduction of antihypertensive medications following Azedra treatment, meeting the pre-defined metric for trial success. There was a correlation between control of hypertension and favorable tumor responses, including radiographic tumor responses, tumor biomarker response and overall survival.

“The positive outcomes from this study indicate the clinical benefit and anti-tumor effects of Azedra,” Dr. Pryma stated in a recent interview. “The clinical response and antitumor effects observed in this heavily pre-treated study population, along with the acceptable adverse event profile from this trial, provide a strong rationale for the future use of Azedra.”

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