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

Primary Purpose

Pheochromocytoma, Paraganglioma

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ultratrace® Iobenguane I131

About this trial

This is an interventional treatment trial for Pheochromocytoma focused on measuring radiotherapy, MIBG, Azedra, neuroendocrine tumors, Iobenguane I 131, progenics

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of California-San Francisco
University of Miami Miller School of Medicine
University of Iowa
Johns Hopkins University
Washington University School of Medicine, Alvin J. Siteman Cancer Center
Mount Sinai School of Medicine
Duke University Medical Center
Hospital of the University of Pennsylvania
Rhode Island Hospital
MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ultratrace® Iobenguane I 131 Treatment

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Patients Who Experienced a 50% or Greater Reduction (Including Discontinuation) of All Antihypertensive Medication(s) Lasting for at Least Six Months.

Secondary Outcome Measures

Best Confirmed Overall Tumor Response of Complete Response (CR) or Partial Response (PR) by RECIST 1.0.

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.

Changes From Baseline in Overall Quality of Life (QoL) - Best Response Within 12 Months After First Therapeutic Dose of AZEDRA®.

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®.

Overall Survival

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.

Full Information

NCT ID

NCT00874614

First Posted

April 1, 2009

Last Updated

February 18, 2020

Sponsor

Molecular Insight Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00874614

Brief Title

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

Official Title

A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 4, 2009 (Actual)

Primary Completion Date

February 14, 2017 (Actual)

Study Completion Date

February 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Molecular Insight Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pheochromocytoma, Paraganglioma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ultratrace® Iobenguane I 131 Treatment

Arm Type

Experimental

Intervention Type

Radiation

Intervention Name(s)

Ultratrace® Iobenguane I131

Other Intervention Name(s)

Azedra®, MIBG

Intervention Description

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.

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Best Confirmed Overall Tumor Response of Complete Response (CR) or Partial Response (PR) by RECIST 1.0.

Description

Time Frame

12 months

Title

Changes From Baseline in Overall Quality of Life (QoL) - Best Response Within 12 Months After First Therapeutic Dose of AZEDRA®.

Description

Time Frame

12 Months

Title

Overall Survival

Description

Time Frame

Up to 5 Years (60 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials: