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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00458952
First received: April 9, 2007
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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


Condition Intervention Phase
Pheochromocytoma
Paraganglioma
Drug: Ultratrace Iobenguane (MIBG) I 131
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Molecular Insight Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Phase1: toxicities (DLTs) in 1st 6 weeks after therapeutic (tx) dose [ Time Frame: 6 weeks post therapy dose ] [ Designated as safety issue: Yes ]
  • Phase2: tumor response by CT/MRI 9 months after tx dose [ Time Frame: 9 months after treatment dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: post therapy ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: post therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 49
Study Start Date: April 2007
Estimated Study Completion Date: May 2013
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
Dosing will begin at 6.0 mCi/kg and will escalate in 1.0 mCi/kg increments until the MTD is established. The MTD is the dose immediately below the level at which escalation stops due to dose-limiting toxicity (DLT). An additional 3 patients are to be treated at the MTD, for a total of 6.
Drug: Ultratrace Iobenguane (MIBG) I 131
Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Iowa
University of Iowa Medical Center
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-0817
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Mallinckrodt Institute of Radiology
St. Louis, Missouri, United States, 63110
United States, New York
New York Presbyterian Hospital-Weill Cornell Medical Center
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 2N8
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5W9
Sponsors and Collaborators
Molecular Insight Pharmaceuticals, Inc.
Investigators
Study Director: Norman LaFrance, MD Molecular Insight Pharmaceuticals
  More Information

No publications provided

Responsible Party: Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00458952     History of Changes
Other Study ID Numbers: MIP-IB12
Study First Received: April 9, 2007
Last Updated: August 1, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Molecular Insight Pharmaceuticals, Inc.:
MIBG
iobenguane
iodine
I 131
radiotherapy
radiopharmaceutical
dosimetry
neuroendocrine tumor
Ultratrace
no carrier added
metaiodobenzyl-guanidine

Additional relevant MeSH terms:
Paraganglioma
Pheochromocytoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
3-Iodobenzylguanidine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014