A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

This clinical trial is designed to evaluate the effectiveness and collect additional safety information on AZEDRA® (iobenguane I 131) for the treatment of metastatic or relapsed/refractory (to other treatment) or unresectable pheochromocytoma or paraganglioma.

The purpose of this trial is to test the use of AZEDRA® as a treatment for pheochromocytoma and paraganglioma, a rare disease. This Phase II study will help determine primarily if using the drug reduces the amount of blood pressure medication being taken as a result of the cancer and secondarily to determine such things as the effectiveness of the study drug in treating the cancer, additional safety measures, and to assess if the drug helps the quality of life and use of pain medication. All subjects will receive an imaging dose with scans followed by two therapeutic doses given approximately 3 months apart.

AZEDRA® (Iobenguane I 131) is a very high-specific-activity iobenguane I 131, produced using proprietary Ultratrace® platform. Based on the well-characterized cellular active transport mechanism, the high specific activity of allows for effective cellular uptake of radioactivity and hence greater tumor uptake.

During this study the subjects will receive two (2) Therapy Doses that are given approximately three (3) months apart. Prior to administration of the first Therapy Dose, subjects will be given an Imaging Dose of AZEDRA® and will undergo iobenguane I 131 scans to evaluate tumor uptake and to measure normal organ distribution and allow for the calculation of radiation dose to normal organs.

Screening procedures for eligibility will need to be done before imaging or therapeutic doses of AZEDRA® are administered.

Hospitalization is required for approximately one (1) week after each of the two (2) Therapeutic Doses. Frequent follow up is necessary for the first year and some of the follow up visits may be done by a visiting health care professional in the subjects' homes. Subjects will be followed in the treatment study for one (1) year and for an additional four (4) years in long-term follow up.

Inclusion Criteria:

• Be at least 12 years of age
• Have a documented (medical record) diagnosis of either pheochromocytoma or paraganglioma
• Be ineligible for curative surgery for pheochromocytoma
• Have failed a prior therapy for pheochromocytoma/paraganglioma or are not candidates for chemotherapy or other curative therapies
• Be on stable antihypertensive medication for pheochromocytoma-related hypertension for at least 30 days
• Have at least one tumor site by CT or MR or iobenguane I 131 scan
• Have an expected survival of at least 6 months
• Subjects must agree to use an acceptable form of birth control (abstinence, IUD, oral contraception, barrier and spermicide or hormonal implant) during this study and for 6 months following Therapeutic Doses of Ultratrace Iobenguane I 131.
• Male subjects must agree not to father a child during the period beginning immediately after administration of the first Therapeutic Dose of Ultratrace Iobenguane I 131 during the study and ending six months after administration of the last Therapeutic Dose of Ultratrace Iobenguane I 131.

Exclusion Criteria:

Subjects will be excluded if any of the following conditions are observed:

• <50% of FDG (if data are available) positive lesions are MIBG avid
• Pregnant or nursing females
• Active CNS lesions by CT/MR scanning within 3 months of study entry
• New York Heart Association class IV heart failure, symptomatic congestive heart failure [New York Heart Association class IV with another medical disorder], unstable angina pectoris, cardiac arrhythmia
• Received any previous systemic radiotherapy resulting in marrow toxicity within 3 months of study entry or have active malignancy (other than pheochromocytoma/paraganglioma) requiring additional treatment during the active phase or follow up period of the Ultratrace® iobenguane I 131 trial.
• Administered prior whole-body radiation therapy
• Received external beam radiotherapy to > 25% of bone marrow
• Administered prior chemotherapy within 30 days or have active malignancy (other than pheochromocytoma/ paraganglioma) requiring additional treatment during the active phase or follow up period of the Ultratrace iobenguane I 131 trial.
• Karnofsky Performance Status is < 60
• Platelets < 80,000/μL
• Absolute neutrophil count (ANC) < 1,200/μL, Total bilirubin > 1.5 times the upper limit of normal, AST/SGOT or ALT/SGPT > 2.5 times the upper limit of normal
• Diagnosed with AIDS or HIV-positive
• Active chronic alcohol abuse, chronic liver disease or hepatitis
• Renal dysfunction/impairment
• Known allergy to iobenguane that has required medical intervention
• Received a therapeutic investigational compound and/or medical device/prior chemotherapy within 30 days before admission into this study
• Receiving a medication which inhibits tumor uptake of iobenguane I 131
• Any medical condition or other circumstances (i.e., uncontrolled current illness including but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with the study requirements.
• Any other condition, that in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study