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

Pheochromocytoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00458952
• Other study ID #: MIP-IB12
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: April 9, 2007
• Last updated: August 1, 2012
• Start date: April 2007
• Est. completion date: May 2013

Study information

• Verified date: August 2012
• Source: Molecular Insight Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: May 2013
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Paraganglioma
• Pheochromocytoma

Intervention

Drug:
• Ultratrace Iobenguane (MIBG) I 131
Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic dose

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Iowa Medical Center	Iowa City	Iowa
United States	Mount Sinai School of Medicine	New York	New York
United States	New York Presbyterian Hospital-Weill Cornell Medical Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Mallinckrodt Institute of Radiology	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Molecular Insight Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase1: toxicities (DLTs) in 1st 6 weeks after therapeutic (tx) dose		6 weeks post therapy dose	Yes
Primary	Phase2: tumor response by CT/MRI 9 months after tx dose		9 months after treatment dose	No
Secondary	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		post therapy	No
Secondary	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		post therapy	No