Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma

A Phase I Study Evaluating the Maximum Tolerated Dose, Dosimetry, Safety, and Efficacy of Ultratrace Iobenguane I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma

The purpose of this study is to determine whether iobenguane I 131 is safe and effective in patients with malignant pheochromocytoma or paraganglioma.

This was originally designed as a phase 1/2 study. The phase 1 patients received a small dose of study drug to see if the tumors absorb the drug. If the patient's tumors absorbed the drug, then the patient received one therapeutic dose. In the phase 1 portion, the study employed a 3 + 3 dose escalation design. Enrollment in the phase 1 portion was to be completed once researches believed that they found the highest dose that they could give patients without causing unacceptable toxicity. This dose is called the maximum tolerated dose (MTD). Following discussions with the Food and Drug Administration (FDA) that occurred during the dose escalation stage of the study, the protocol was amended to conclude the trial upon the identification of the MTD. The Phase 2 safety/ efficacy stage of the study was conducted with modifications of the primary endpoint as Protocol MIP IB12B, with Special Protocol Assessment Agreement with the FDA in March 2009.

Inclusion Criteria:

• Have a diagnosis of either adrenal pheochromocytoma or extra-adrenal paraganglioma by histological confirmation OR plasma-free metanephrines and 24-hour urine test for catecholamines/ metanephrines
• Disease is metastatic or has recurred following surgery
• At least one measurable lesion seen by computed tomography (CT) or magnetic resonance (MR) scan performed within 4 weeks prior to the first dose of study drug
• At least one known tumor site is also seen on Ultratrace iobenguane I 131 scan
• Provide written informed consent and are willing to comply with protocol requirements
• Are at least 18 years of age
• If female, then not of childbearing potential as documented by history (e.g., tubal ligation or hysterectomy) or is post menopausal with a minimum 1 year without menses
• If female of childbearing potential, has a negative serum b-HCG pregnancy test within 48 hours prior to receiving iobenguane I 131
• Females who agree not to become pregnant and males who agree not to father a child during the 1 year period following the therapeutic dose of Ultratrace iobenguane I 131. Both females and males must use an acceptable method of birth control during the first year following the therapeutic dose of Ultratrace iobenguane I 131.

Exclusion Criteria:

• Females who are nursing
• Active CNS lesions by CT/MR scanning within 3 months of study entry
• New York Heart Association class III-IV heart failure
• Received any previous systemic radiotherapy within 6 months of study entry
• Administered prior whole-body radiation therapy
• Received external beam radiotherapy to greater than 25 percent of bone marrow
• Administered prior chemotherapy within 30 days of study entry
• Karnofsky performance status is less than 60
• Platelets are less than 100,000/uL
• Absolute neutrophil count (ANC) is less than 1,500/uL
• Serum creatinine is greater than 1.5 mg/dL
• Total bilirubin is greater than 1.5 times the upper limit of normal
• AST/SGOT or ALT/SGPT is greater than 2.5 times the upper limit of normal
• Has received a therapeutic investigational compound and/or medical device within 30 days before admission into this study
• Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post dose follow-up examinations
• Is determined by the Investigator that the patient is clinically unsuitable for the study.
• Has received a medication which inhibits uptake of iobenguane I 131:
• phenothiazines or decongestants within 2 weeks prior to enrollment; or,
• a tricyclic antidepressant within 6 weeks prior to enrollment.