Phase 1-2 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma

Condition(s) targeted: Pheochromocytoma; Paraganglioma

Intervention: Ultratrace Iobenguane (MIBG) I 131 (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Molecular Insight Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Norman LaFrance, MD, Study Director, Affiliation: Molecular Insight Pharmaceuticals

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

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

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

Primary outcome:

Phase1: toxicities (DLTs) in 1st 6 weeks after therapeutic (tx) dose

Phase2: tumor response by CT/MRI 9 months after tx dose

Secondary outcome:

Phase1: 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

Phase2: 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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Cross Cancer Institute, Edmonton, Alberta T6G 2N8, Canada; Not yet recruiting
Margaret Landon, Phone: 780-432-8751, Email: margland@cancerboard.ab.ca
Gail Amyotte, Phone: 780-432-8202, Email: gaila@cancerboard.ab.ca
Alexander J. McEwan, M.D., Principal Investigator

University of Iowa Medical Center, Iowa City, Iowa 52242, United States; Not yet recruiting
Stacy Michael, Phone: 319-335-8966, Email: stacy-michael@uiowa.edu
Thomas O'Dorisio, M.D., Phone: 319-353-7812, Email: thomas-odorisio@uiowa.edu
Thomas O'Dorisio, M.D., Principal Investigator

Johns Hopkins University, Baltimore, Maryland 21287-0817, United States; Not yet recruiting
Yetty Olagbemiro, Email: yolagbe1@jhmi.edu
Nicole Cooper, Email: ncooper2@jhmi.edu
Richard L. Wahl, M.D., Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Not yet recruiting
Terry Brinkman, Phone: 507-266-8330, Email: brinkman.terry@mayo.edu
Gregory Wiseman, Phone: 507-284-9599, Email: gwiseman@mayo.edu
Gregory Wiseman, M.D., Principal Investigator

Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110, United States; Not yet recruiting
Jennifer Frye, Phone: 314-747-1604, Email: fryej@mir.wustl.edu
Perry W. Grigsby, M.D., Phone: 314-362-8502, Email: pgrigsby@radonc.wustl.edu
Perry W. Grigsby, M.D., Principal Investigator

New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York 10021, United States; Recruiting
Shankar Vallabhajosula, M.D., Phone: 212-746-5694, Email: svallabh@med.cornell.edu
Zubaida Rahman, R.Ph., Email: zur9002@nyp.org
Stanley Goldsmith, M.D., Principal Investigator

Mount Sinai School of Medicine, New York, New York 10029, United States; Not yet recruiting
Lale Kostakoglu, M.D., Phone: 212-241-6319, Email: lale.kostakoglu@msnyuhealth.org
Lale Kostakoglu, M.D., Principal Investigator

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Edward Coleman, M.D., Phone: 919-684-7244, Email: colem010@mc.duke.edu
Beth Parente, Phone: 919-970-1467, Email: beth.parente@duke.edu
Edward Coleman, M.D., Principal Investigator

London Health Sciences Centre, London, Ontario N6A 5W9, Canada; Not yet recruiting
Patty Laverty, Phone: (519)685-8500, Ext: 76068, Email: Patricia.Laverty@lhsc.on.ca
Susan Vandermark, Email: Susan.Vandermark@lhsc.on.ca
Robert Reid, M.D., Principal Investigator

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Not yet recruiting
Alex Wills, Phone: 215-662-3049, Email: eze.wills@uphs.upenn.edu
Chaitanya Divgi, M.D., Phone: 215-615-3687, Email: chaitanya.divgi@uphs.upenn.edu
Chaitanya Divgi, M.D., Principal Investigator

Rhode Island Hospital, Providence, Rhode Island 02903, United States; Recruiting
Elizabeth Morrell, Phone: 401-444-2277, Email: emorrell@lifespan.org
Richard B. Noto, M.D., Phone: 401-444-5184, Email: rnoto@lifespan.org
Richard B. Noto, M.D., Principal Investigator

Starting date: April 2007
Ending date: April 2012
Last updated: December 8, 2007