PheochromocytomaPhase 1/2NCT00458952
Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
A Phase 1/2 study testing Ultratrace Iobenguane (MIBG) I 131 in people with Pheochromocytoma and Paraganglioma, run by Molecular Insight Pharmaceuticals, Inc. at 3 sites in United States.
Trial summary
The purpose of this study is to determine whether iobenguane I 131 is safe and effective in patients with malignant pheochromocytoma or paraganglioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pheochromocytoma, Paraganglioma
- What is being tested?
- Ultratrace Iobenguane (MIBG) I 131
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2007to Jun 2011
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Duke University Medical Center
Durham, North Carolina, 27710
New York Presbyterian Hospital-Weill Cornell Medical Center
New York, New York, 10021
Rhode Island Hospital
Providence, Rhode Island, 02903
About this study
Official title: A Phase I Study Evaluating the Maximum Tolerated Dose, Dosimetry, Safety, and Efficacy of Ultratrace Iobenguane I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
The purpose of this study is to determine whether iobenguane I 131 is safe and effective in patients with malignant pheochromocytoma or paraganglioma.
Read the detailed description
This was originally designed as a phase 1/2 study. The phase 1 patients received a small dose of study drug to see if the tumors absorb the drug. If the patient's tumors absorbed the drug, then the patient received one therapeutic dose. In the phase 1 portion, the study employed a 3 + 3 dose escalation design. Enrollment in the phase 1 portion was to be completed once researches believed that they found the highest dose that they could give patients without causing unacceptable toxicity. This dose is called the maximum tolerated dose (MTD). Following discussions with the Food and Drug Administration (FDA) that occurred during the dose escalation stage of the study, the protocol was amended to conclude the trial upon the identification of the MTD. The Phase 2 safety/ efficacy stage of the study was conducted with modifications of the primary endpoint as Protocol MIP IB12B, with Special Protocol Assessment Agreement with the FDA in March 2009.
- Conditions
- Pheochromocytoma, Paraganglioma
- Being tested
- Ultratrace Iobenguane (MIBG) I 131
- Keywords
- MIBG, iobenguane, iodine, I 131, radiotherapy, radiopharmaceutical, dosimetry, neuroendocrine tumor, Ultratrace, no carrier added, metaiodobenzyl-guanidine
- 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 (MIBG) I 131Drug
Also called Ultratrace Iobenguane I 131, Azedra Ultratrace (iobenguane I 131)
Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic dose
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Dosing of Ultratrace iobenguane I 131 began at 6.0 mCi/kg and escalated in 1.0 mCi/kg increments in order to establish the MTD. 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. Receives: Drug: Ultratrace Iobenguane (MIBG) I 131 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Ultratrace Iobenguane I 131
Although no primary efficacy endpoint was defined for this study, the MTD of Ultratrace iobenguane I 131 in patients with malignant pheochromocytoma/paraganglioma (a safety rather than an efficacy parameter) is the primary objective.
Measured: 6 weeks post therapy dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionJun 2009
- Study completionJun 2011
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Molecular Insight Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Molecular Insight Pharmaceuticals, Study director, MIP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458952
- Sponsor's protocol ID
- MIP-IB12
- Status last verified
- Jun 2016
- First submitted
- 9 Apr 2007
- Last updated
- 13 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Noto RB, Pryma DA, Jensen J, Lin T, Stambler N, Strack T, Wong V, Goldsmith SJ. Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma. J Clin Endocrinol Metab. 2018 Jan 1;103(1):213-220. doi: 10.1210/jc.2017-02030.
PubMed 29099942
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating the Maximum Tolerated Dose, Dosimetry, Safety, and Efficacy of Ultratrace Iobenguane I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
- ClinicalTrials.gov ID
- NCT00458952
- Acronym / sponsor ID
- MIP-IB12
- Conditions
- Pheochromocytoma, Paraganglioma
- Keywords
- MIBG, iobenguane, iodine, I 131, radiotherapy, radiopharmaceutical, dosimetry, neuroendocrine tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Molecular Insight Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 11 Apr 2007 (estimated)
- Results
- Posted 20 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether iobenguane I 131 is safe and effective in patients with malignant pheochromocytoma or paraganglioma.
Detailed description
This was originally designed as a phase 1/2 study. The phase 1 patients received a small dose of study drug to see if the tumors absorb the drug. If the patient's tumors absorbed the drug, then the patient received one therapeutic dose. In the phase 1 portion, the study employed a 3 + 3 dose escalation design. Enrollment in the phase 1 portion was to be completed once researches believed that they found the highest dose that they could give patients without causing unacceptable toxicity. This dose is called the maximum tolerated dose (MTD). Following discussions with the Food and Drug Administration (FDA) that occurred during the dose escalation stage of the study, the protocol was amended to conclude the trial upon the identification of the MTD. The Phase 2 safety/ efficacy stage of the study was conducted with modifications of the primary endpoint as Protocol MIP IB12B, with Special Protocol Assessment Agreement with the FDA in March 2009.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: Ultratrace Iobenguane (MIBG) I 131Dosing of Ultratrace iobenguane I 131 began at 6.0 mCi/kg and escalated in 1.0 mCi/kg increments in order to establish the MTD. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (19 listed)
- 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
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 (MIBG) I 131Also: Ultratrace Iobenguane I 131, Azedra Ultratrace (iobenguane I 131)Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic dose | Drug | Dose Escalation |
Primary outcome
MTD of Ultratrace Iobenguane I 131
Time frame: 6 weeks post therapy dose
Although no primary efficacy endpoint was defined for this study, the MTD of Ultratrace iobenguane I 131 in patients with malignant pheochromocytoma/paraganglioma (a safety rather than an efficacy parameter) is the primary objective.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29099942Noto RB, Pryma DA, Jensen J, Lin T, Stambler N, Strack T, Wong V, Goldsmith SJ. Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma. J Clin Endocrinol Metab. 2018 Jan 1;103(1):213-220. doi: 10.1210/jc.2017-02030.
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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.
Molecular Insight Pharmaceuticals study director
MIP
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ultratrace Iobenguane (MIBG) I 131 in people with Pheochromocytoma and Paraganglioma, run by Molecular Insight Pharmaceuticals, Inc. at 3 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 19 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: finished, as of the sponsor's last update on 13 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 Apr 2016). 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?
MTD of Ultratrace Iobenguane I 131 (time frame: 6 weeks post therapy dose). 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 NCT00458952, 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 13 Jul 2016.