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

This study is open for patient recruitment

Purpose

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

MedlinePlus related topics: Cancer; Pheochromocytoma
Genetics Home Reference related topics: Pheochromocytoma

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

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

Primary Outcome Measures:

• Phase 1: toxicities (DLTs) in 1st six weeks after therapeutic (tx) dose
• Phase 2: tumor response by CT/MRI nine months after tx dose

Secondary Outcome Measures:

• Phase 1: radiation absorbed 1 hour after dose 1(small dose), 2-4 days after dose 1, and 5-7 days after dose 1; tumor response by CT/MRI & blood/urine tests 3, 6, 9, & 12 months after tx dose; dose response by CT/MRI 9 months after tx dose
• Phase 2: tumor response by CT/MRI & blood/urine tests 3, 6, 9, & 12 month after tx dose; quality of life 3, 6, 9, & 12 months after tx dose

Expected Total Enrollment: 37

Study start: April 2007; Expected completion: July 2012

This is a phase 1 and phase 2 study. The phase 1 patients will be enrolled before the phase 2 patients are enrolled. Each patient will receive a small dose to see if the tumors absorb the drug. If the patient's tumors absorb the drug, then the patient will receive one therapeutic dose. In the phase 1 portion, every 3 patients will be given the same therapeutic dose, and usually each group of 3 patients will be given a larger dose than people who were enrolled before them. Enrollment in the phase 1 portion will be complete once researches believe that they have found the highest dose that they can give patients without causing unacceptable toxicity. This dose is called the maximum tolerated dose (MTD). All phase 2 patients will receive the MTD. Each patient in phase 1 and phase 2 will be followed for 5 years following their therapeutic dose. During this 5-year follow-up period, patients will undergo tests such as 1.) CT or MRI scans and blood and urine tests to determine if the tumors shrink, grow, or stay the same; 2.) bone scans to see if the tumor has spread to or increased in the bones and, 3.) a quality of life test to see how the symptoms of pheochromocytoma or paraganglioma affect patients' daily lives.

Eligibility

Ages Eligible for Study: 18 Years and above
Genders Eligible for Study: Both

Inclusion Criteria:
Patients must meet all of the following 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 ?-HCG pregnancy test serum 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:
Patients will be excluded if any of the following conditions are observed:

• 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 > 25% of bone marrow
• Administered prior chemotherapy within 30 days of study entry
• Karnofsky performance status is < 60
• Platelets ? 100,000/?L
• Absolute neutrophil count (ANC) ? 1,500/?L
• Serum creatinine ? 1.5 mg/dL
• Total bilirubin ? 1.5 times the upper limit of normal
• AST/SGOT or ALT/SGPT ? 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
• Has evidence of altered biodistribution of Ultratrace iobenguane I 131
• Has evidence of renal obstruction
• 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 the first dose of Ultratrace iobenguane I 131; or, a tricyclic antidepressant within 6 weeks prior to the first dose of Ultratrace iobenguane I 131, or labetelol within 1 week prior to the first dose of Ultratrace iobenguane I 131

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier: NCT00458952

More Information

Study ID Numbers: MIP-IB12
ClinicalTrials.gov Identifier: NCT00458952
Health Authority: United States: Food and Drug Administration; Canada: Health Canada