PheochromocytomaPhase 2NCT00874614
A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
A Phase 2 study testing Ultratrace® Iobenguane I131 in people with Pheochromocytoma and Paraganglioma, run by Molecular Insight Pharmaceuticals, Inc. at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pheochromocytoma, Paraganglioma
- What is being tested?
- Ultratrace® Iobenguane I131
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 10 sitesUnited States
- Study dates
- 4 Jun 2009to Feb 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins University
Baltimore, Maryland, 21287
Duke University Medical Center
Durham, North Carolina, 27710
MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Miami Miller School of Medicine
Miami, Florida, 33136
Mount Sinai School of Medicine
New York, New York, 10029
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Rhode Island Hospital
Providence, Rhode Island, 02903
University of California-San Francisco
San Francisco, California, 94143
Washington University School of Medicine, Alvin J. Siteman Cancer Center
St Louis, Missouri, 63110
About this study
Official title: A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
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.
Read the 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.
- Conditions
- Pheochromocytoma, Paraganglioma
- Being tested
- Ultratrace® Iobenguane I131
- Keywords
- radiotherapy, MIBG, Azedra, neuroendocrine tumors, Iobenguane I 131, progenics
- Medical subject headings
- Pheochromocytoma, Paraganglioma, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultratrace® Iobenguane I131Radiation
Also called Azedra®, MIBG
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.
| Study group | Role | What they receive |
|---|---|---|
| Ultratrace® Iobenguane I 131 Treatment | Experimental | Not described Receives: Radiation: Ultratrace® Iobenguane I131 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Who Experienced a 50% or Greater Reduction (Including Discontinuation) of All Antihypertensive Medication(s) Lasting for at Least Six Months.
Measured: 12 months
Secondary outcomes (3)
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.
Measured: 12 months
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®.
Measured: 12 Months
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.
Measured: Up to 5 Years (60 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2009 (estimated)
- Study start4 Jun 2009
- Primary completion14 Feb 2017
- Study completionFeb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PheochromocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Molecular Insight Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bennett Chin, MD, Principal investigator, Duke UniversityDaniel Pryma, MD, Principal investigator, University of PennsylvaniaJeffrey Olsen, MD, Principal investigator, Mallinckrodt Institute of Radiology Washington UniversityCamillo Jimenez, MD, Principal investigator, MD Anderson CancerJoseph Dillon, MD, Principal investigator, University of IowaLilja Solnes, MD, Principal investigator, Johns Hopkins UniversityLale Kostakoglu, MD, Principal investigator, Icahn School of Medicine at Mount SinaiMichael H Pampaloni, MD, Principal investigator, University of California at San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00874614
- Sponsor's protocol ID
- MIP-IB12B
- Status last verified
- Feb 2020
- First submitted
- 1 Apr 2009
- Last updated
- 20 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
- Expanded access
- Available
Publications
Jimenez C, Chin BB, Noto RB, Dillon JS, Solnes L, Stambler N, DiPippo VA, Pryma DA. Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma. Endocr Relat Cancer. 2023 Jan 5;30(2):e220236. doi: 10.1530/ERC-22-0236. Print 2023 Feb 1.
PubMed 36472300
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
- ClinicalTrials.gov ID
- NCT00874614
- Acronym / sponsor ID
- MIP-IB12B
- Conditions
- Pheochromocytoma, Paraganglioma
- Keywords
- radiotherapy, MIBG, Azedra, neuroendocrine tumors, Iobenguane I 131, progenics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Molecular Insight Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Jun 2009 (actual)
- Primary completion
- 14 Feb 2017 (actual)
- Study completion
- Feb 2021 (estimated)
- First posted
- 2 Apr 2009 (estimated)
- Results
- Posted 5 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ultratrace® Iobenguane I 131 Treatment | Experimental | Radiation: Ultratrace® Iobenguane I131 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (20 listed)
- <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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ultratrace® Iobenguane I131Also: Azedra®, MIBGEach 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. | Radiation | Ultratrace® Iobenguane I 131 Treatment |
Primary outcome
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
3 secondary outcomes
Best Confirmed Overall Tumor Response of Complete Response (CR) or Partial Response (PR) by RECIST 1.0.
Time frame: 12 months
Changes From Baseline in Overall Quality of Life (QoL) - Best Response Within 12 Months After First Therapeutic Dose of AZEDRA®.
Time frame: 12 Months
Overall Survival
Time frame: Up to 5 Years (60 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36472300Jimenez C, Chin BB, Noto RB, Dillon JS, Solnes L, Stambler N, DiPippo VA, Pryma DA. Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma. Endocr Relat Cancer. 2023 Jan 5;30(2):e220236. doi: 10.1530/ERC-22-0236. Print 2023 Feb 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bennett Chin, MD principal investigator
Duke University
Daniel Pryma, MD principal investigator
University of Pennsylvania
Jeffrey Olsen, MD principal investigator
Mallinckrodt Institute of Radiology Washington University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ultratrace® Iobenguane I131 in people with Pheochromocytoma and Paraganglioma, run by Molecular Insight Pharmaceuticals, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00874614, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.