A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

• ClinicalTrials.gov Identifier: NCT00874614
• Recruitment Status: Unknown
• First Posted: April 2, 2009
• Results First Posted: October 5, 2018
• Last Update Posted: February 20, 2020
• Sponsor: Molecular Insight Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Molecular Insight Pharmaceuticals, Inc.

Study Description

Brief Summary:

This clinical trial is designed to evaluate the effectiveness and collect additional safety information on AZEDRA® (iobenguane I 131) for the treatment of metastatic or relapsed/refractory (to other treatment) or unresectable pheochromocytoma or paraganglioma.

The purpose of this trial is to test the use of AZEDRA® as a treatment for pheochromocytoma and paraganglioma, a rare disease. 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 therapeutic doses given approximately 3 months apart.

Condition or disease	Intervention/treatment	Phase
Pheochromocytoma; Paraganglioma	Radiation: Ultratrace® Iobenguane I131	Phase 2

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Detailed Description:

AZEDRA® (Iobenguane I 131) is a very high-specific-activity iobenguane I 131, produced using proprietary Ultratrace® platform. Based on the well-characterized cellular active transport mechanism, the high specific activity of allows for effective cellular uptake of radioactivity and hence greater tumor uptake.

During this study the subjects will receive two (2) Therapy Doses that are given approximately three (3) months apart. Prior to administration of the first Therapy Dose, subjects will be given an Imaging Dose of AZEDRA® 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 AZEDRA® 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 74 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: June 4, 2009
• Actual Primary Completion Date: February 14, 2017
• Estimated Study Completion Date: February 2021

Arms and Interventions

Arm

Intervention/treatment

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 Names: Azedra®; MIBG

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Who Experienced a 50% or Greater Reduction (Including Discontinuation) of All Antihypertensive Medication(s) Lasting for at Least Six Months. [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. Best Confirmed Overall Tumor Response of Complete Response (CR) or Partial Response (PR) by RECIST 1.0. [ Time Frame: 12 months ]
   Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 was assessed by two independent central reviewers and one adjudicator, and overall response (PR or CR) was confirmed by follow-up imaging at the subsequent timepoint. Complete response was defined as confirmed disappearance of all target lesions and Partial Response was defined as confirmed decreased of >= 30% in baseline sum of the longest diameter of target lesions.
2. Changes From Baseline in Overall Quality of Life (QoL) - Best Response Within 12 Months After First Therapeutic Dose of AZEDRA®. [ Time Frame: 12 Months ]
   The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 v.3 was used to evaluate QoL. This questionnaire was comprised of 30 questions, two of which pertain to a patient's Global Health Status and QoL. The two questions used a 7-point Likert scale of 1 (very poor) to 7 (excellent), in which the scores were averaged and linearly transformed to a 0-100 scale with higher scores indicating better health status and QoL. The questionnaire was administered at baseline and through 12 months after the first therapeutic dose of AZEDRA®. The results of QoL and changes from baseline were summarized by visit and the best response within 12 months after first therapeutic dose of AZEDRA® was reported. The outcome represents the mean change from baseline in overall QoL based on the best response reported within 12 months after first therapeutic dose of AZEDRA®.
3. Overall Survival [ Time Frame: Up to 5 Years (60 months) ]
   Duration of overall survival was calculated from the date of first therapeutic dose of AZEDRA® to death, or at the last date the patient was known to be alive. Results are presented per December 2017 data-cut. Survival was censored at the end of the 5-year long-term follow-up period, thus the upper limit of the confidence interval reported below for two therapeutic doses is actually >60 months.

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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
• 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

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, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Missouri

Washington University School of Medicine, Alvin J. Siteman Cancer Center

Saint 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: Bennett Chin, MD; Duke University
• Principal Investigator: Daniel Pryma, MD; University of Pennsylvania
• Principal Investigator: Jeffrey Olsen, MD; Mallinckrodt Institute of Radiology Washington University
• Principal Investigator: Camillo Jimenez, MD; MD Anderson Cancer
• Principal Investigator: Joseph Dillon, MD; University of Iowa
• Principal Investigator: Lilja Solnes, MD; Johns Hopkins University
• Principal Investigator: Lale Kostakoglu, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Michael H Pampaloni, MD; University of California at San Francisco

  Study Documents (Full-Text)

Documents provided by Molecular Insight Pharmaceuticals, Inc.:

Study Protocol  [PDF] March 21, 2014

Statistical Analysis Plan  [PDF] March 6, 2017

More Information

• Responsible Party: Molecular Insight Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00874614
• Other Study ID Numbers: MIP-IB12B
• First Posted: April 2, 2009
• Results First Posted: October 5, 2018
• Last Update Posted: February 20, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Molecular Insight Pharmaceuticals, Inc.:

radiotherapy; MIBG; Azedra; neuroendocrine tumors; Iobenguane I 131; progenics

Additional relevant MeSH terms:

Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; 3-Iodobenzylguanidine; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals