Expanded Access Program of Ultratrace Iobenguane I131 for Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

Expanded Access Program of AZEDRA (Ultratrace Iobenguane I131) in Subjects With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma: A Sub-study of Protocol MIP-IB12B

The purpose of this sub-study is to provide expanded access of AZEDRA (Ultratrace Iobenguane I 131) and to evaluate the safety and tolerability of AZEDRA in subjects with iobenguane-avid malignant and/or recurrent pheochromocytoma/paraganglioma (PPGL).

MIP-IB12B, the pivotal phase 2 study evaluating efficacy and safety of AZEDRA in patients with malignant relapsed/refractory PPGL, has completed its anticipated enrollment. The purpose of this sub-study, MIP-IB12B-EAP, is to provide expanded access to AZEDRA for newly enrolled subjects with iobenguane-avid metastatic and/or recurrent PPGL and to collect additional safety data.

Inclusion Criteria:

• Able and willing to provide informed consent/assent and comply with protocol requirements
• Documented diagnosis of either pheochromocytoma or paraganglioma that was confirmed by histology or other supportive data (e.g. abnormal MIBG diagnostic study or elevated tumor markers)
• Ineligible for curative surgery for PPGL
• Failed a prior therapy for PPGL or have no alternative indicated therapy available
• Have definitive tumor avidity confirmed by the AZEDRA dosimetry dose
• Life expectancy of at least 6 months per physician

Exclusion Criteria:

• Pregnant or nursing females
• Men or women of childbearing potential and unwilling to use a medically acceptable form of contraception from time of consent until 6 months following last therapeutic dose of AZEDRA
• Active CNS lesions by CT/MRI within 3 months of informed consent
• NYHA class IV heart failure, unstable angina pectoris or clinically significant cardiac arrhythmia that poses a risk of syncope or cardiac arrest
• Prior systemic radiotherapy resulting in marrow toxicity within 3 months of first AZEDRA therapeutic dose
• Prior iobenguane I 131 therapeutic exposure within 12 weeks of the first planned therapeutic dose
• Prior administration of whole-body radiation therapy within 12 weeks of the first planned therapeutic dose
• Prior external beam radiotherapy to > 25% of bone marrow
• Prior chemotherapy or investigational compound and/or device within 30 days of the dosimetry dose
• Other active malignancy requiring additional treatment except for superficial cutaneous neoplasms
• Karnofsky Performance Status < 60
• Clinically significant laboratory abnormalities prior to dosing as listed in the protocol (such as blood count abnormalities, liver enzyme abnormalities, and renal dysfunction)
• Medical history of AIDS/HIV+
• Active chronic alcohol abuse, chronic liver disease (not including liver metastases), hepatitis A, B, or C
• Known allergy to iobenguane that has required medical intervention
• Receiving a medication which inhibits tumor uptake of iobenguane I 131
• Any other condition, that in the opinion of the investigator, may compromise the safety or compliance of the subject