A Study Evaluating Ultratrace Iobenguane I 131(MIBG)in Patients With Malignant Pheochromocytoma/Paraganglioma - Full Text View

Sponsor:	Molecular Insight Pharmaceuticals, Inc.
Information provided by:	Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00874614

Purpose

This clinical trial is designed to evaluate the effectiveness and collect additional safety information on Ultratrace Iobenguane I 131 for the treatment of relapsed/refractory (to other treatment) malignant pheochromocytoma and paraganglioma.

The purpose of this trial is to test the use of Ultratrace iobenguane I 131 as a treatment for pheochromocytoma and paraganglioma type cancer. This Phase II study will help determine primarily if using the drug reduces the amount of blood pressure medication being taken as a result of the cancer and secondarily to determine such things as the effectiveness of the study drug in treating the cancer, additional safety measures and to assess if the drug helps the quality of life and use of pain medication. All subjects will receive an imaging dose with scans followed by two therapy doses that are given 3 months apart.

Condition	Intervention	Phase
Pheochromocytoma Paraganglioma	Radiation: Ultratrace Iobenguane I131	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary paraganglioma-pheochromocytoma nonsyndromic paraganglioma

MedlinePlus related topics: Cancer Pheochromocytoma

Drug Information available for: Sodium iodide I 131

U.S. FDA Resources

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

Primary Outcome Measures:

Proportion of study subjects with a reduction (including discontinuation) of all antihypertensive medication by at least 50% for at least six months or two cycles Ultratrace Iobenguane I 131. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects with overall tumor response of Complete Response or Partial Response by RECIST criteria [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
Safety assessed by changes in lab values, physical exams or vital signs, and the occurrence of treatment emergent adverse events [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	75
Study Start Date:	June 2009
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ultratrace Iobenguane I 131 Treatment	Radiation: Ultratrace Iobenguane I131 Each subject will be administered 3 mCi to 6 mCi Ultratrace Iobenguane I 131, referred to as the Imaging Dose, to confirm that subject meets radiological entry criteria and to establish dosimetry. All subjects meeting entry criteria will then receive the investigational product referred to as the Therapeutic Dose (500 mCi or 8 mCi/kg if the subject weighs 62.5 kg or less) of Ultratrace Iobenguane I 131, followed by imaging at 7 days post infusion or upon discharge from isolation. The Therapeutic Doses will be adjusted equally if warranted by results of the dosimetry evaluation. At least 3 months later, subjects will receive the second Therapeutic Dose. Other Name: Azedra

Arms

Assigned Interventions

Experimental: Ultratrace Iobenguane I 131 Treatment

Radiation: Ultratrace Iobenguane I131

Each subject will be administered 3 mCi to 6 mCi Ultratrace Iobenguane I 131, referred to as the Imaging Dose, to confirm that subject meets radiological entry criteria and to establish dosimetry. All subjects meeting entry criteria will then receive the investigational product referred to as the Therapeutic Dose (500 mCi or 8 mCi/kg if the subject weighs 62.5 kg or less) of Ultratrace Iobenguane I 131, followed by imaging at 7 days post infusion or upon discharge from isolation. The Therapeutic Doses will be adjusted equally if warranted by results of the dosimetry evaluation. At least 3 months later, subjects will receive the second Therapeutic Dose.

Other Name: Azedra

Detailed Description:

Azedra™ Ultratrace™ (Iobenguane I 131), commonly referred to as Ultratrace Iobenguane I 131, is a very high specific activity form of iobenguane I 131, produced using Molecular Insight's proprietary Ultratrace™ platform. Based on the well characterized cellular active transport mechanism, the higher the specific activity of iobenguane I 131, the greater the cellular uptake of radioactivity and hence greater tumor uptake.

During this study the subjects will receive two (2) Therapy Doses that are given three (3) months apart. Prior to administration of the first Therapy Dose, subjects will be given an Imaging Dose of Ultratrace Iobenguane I 131 and will undergo iobenguane I 131 scans to evaluate tumor uptake and to measure normal organ distribution and allow for the calculation of radiation dose to normal organs.

Screening procedures for eligibility will need to be done before imaging or therapeutic doses of Iobenguane I 131 are administered.

Hospitalization is required for approximately one (1) week after each of the two (2) Therapeutic Doses. Frequent follow up is necessary for the first year and some of the follow up visits may be done by a visiting health care professional in the subjects' homes. Subjects will be followed in the treatment study for one (1) year and for an additional four (4) years in long-term follow up.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Be at least 12 years of age
Have a documented (medical record) diagnosis of either pheochromocytoma or paraganglioma with histological confirmation
Be ineligible for curative surgery for pheochromocytoma
Have failed a prior therapy for pheochromocytoma/paraganglioma or are not candidates for chemotherapy or other curative therapies
Be on stable antihypertensive medication for pheochromocytoma-related hypertension for at least 30 days
Have at least one tumor site by CT or MR or iobenguane I 131 scan
Have an expected survival of at least 6 months
Subjects must agree to use an acceptable form of birth control (abstinence, IUD, oral contraception, barrier and spermicide or hormonal implant) during this study and for 6 months following Therapeutic Doses of Ultratrace Iobenguane I 131.
Male subjects must agree not to father a child during the period beginning immediately after administration of the first Therapeutic Dose of Ultratrace Iobenguane I 131 during the study and ending six months after administration of the last Therapeutic Dose of Ultratrace Iobenguane I 131.

Exclusion Criteria:

Subjects will be excluded if any of the following conditions are observed:

<50% of FDG (if data are available) positive lesions are MIBG avid
Pregnant or nursing females
Active CNS lesions by CT/MR scanning within 3 months of study entry
New York Heart Association class IV heart failure, symptomatic congestive heart failure [New York Heart Association class IV with another medical disorder], unstable angina pectoris, cardiac arrhythmia
Received any previous systemic radiotherapy resulting in marrow toxicity within 3 months of study entry or have active malignancy (other than pheochromocytoma/paraganglioma) requiring additional treatment during the active phase or follow up period of the Ultratrace iobenguane I 131 trial.
Administered prior whole-body radiation therapy
Received external beam radiotherapy to > 25% of bone marrow
Administered prior chemotherapy within 30 days or have active malignancy (other than pheochromocytoma/ paraganglioma) requiring additional treatment during the active phase or follow up period of the Ultratrace iobenguane I 131 trial.
Karnofsky Performance Status is < 60
Platelets < 80,000/μL
Absolute neutrophil count (ANC) < 1,200/μL, Total bilirubin > 1.5 times the upper limit of normal, AST/SGOT or ALT/SGPT > 2.5 times the upper limit of normal
Diagnosed with AIDS or HIV-positive
Active chronic alcohol abuse, chronic liver disease or hepatitis
Renal dysfunction/impairment
Known allergy to iobenguane that has required medical intervention
Received a therapeutic investigational compound and/or medical device/prior chemotherapy within 30 days before admission into this study
Receiving a medication which inhibits tumor uptake of iobenguane I 131
Any medical condition or other circumstances (i.e., uncontrolled current illness including but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with the study requirements.
Any other condition, that in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874614

Locations

United States, California
University of California-San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Louisiana
Louisana State University Health Sciences Center
Kenner, Louisiana, United States, 70065
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine, Alvin J. Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, New York
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
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

Molecular Insight Pharmaceuticals, Inc.

Investigators

Principal Investigator:	Edward Coleman, MD	Duke University
Principal Investigator:	Lowell Anthony, MD	Louisana State University Health Center
Principal Investigator:	Daniel Pryma, MD	University of Pennsylvania
Principal Investigator:	Perry W Grigsby, MD	Mallinckrodt Institute of Radiology Washington University
Principal Investigator:	Camillo Jimenez, MD	MD Anderson Cancer
Principal Investigator:	Richard Noto, MD	Rhode Island Hospital
Principal Investigator:	Thomas O'Dorisio, MD	University of Iowa
Principal Investigator:	Richard Wahl, MD	Johns Hopkins University
Principal Investigator:	Lale Kostakoglu, MD	Mount Sinai School of Medicine
Principal Investigator:	Aldo Serafini, MD	University of Miami
Principal Investigator:	Miguel Pampaloni, MD PhD	University of California, San Francisco

More Information

No publications provided

Responsible Party:	Norman LaFrance/Chief Medical Officer and Senior VP, Molecular Insight Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00874614 History of Changes
Other Study ID Numbers:	MIP-IB12B
Study First Received:	April 1, 2009
Last Updated:	June 6, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Molecular Insight Pharmaceuticals, Inc.:

radiotherapy
MIBG
Azedra
neuroendocrine tumors

paraganglioma
pheochromocytoma
Iobenguane I 131

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 May 23, 2012