Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
Primary Purpose
Pheochromocytoma, Paraganglioma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ultratrace Iobenguane (MIBG) I 131
Sponsored by
About this trial
This is an interventional treatment trial for Pheochromocytoma focused on measuring MIBG, iobenguane, iodine, I 131, radiotherapy, radiopharmaceutical, dosimetry, neuroendocrine tumor, Ultratrace, no carrier added, metaiodobenzyl-guanidine
Eligibility Criteria
Inclusion Criteria:
- 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
- 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.
Exclusion Criteria:
- 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
- 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.
Sites / Locations
- New York Presbyterian Hospital-Weill Cornell Medical Center
- Duke University Medical Center
- Rhode Island Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT00458952
First Posted
April 9, 2007
Last Updated
June 13, 2016
Sponsor
Molecular Insight Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00458952
Brief Title
Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Molecular Insight Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pheochromocytoma, Paraganglioma
Keywords
MIBG, iobenguane, iodine, I 131, radiotherapy, radiopharmaceutical, dosimetry, neuroendocrine tumor, Ultratrace, no carrier added, metaiodobenzyl-guanidine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ultratrace Iobenguane (MIBG) I 131
Other Intervention Name(s)
Ultratrace Iobenguane I 131, Azedra Ultratrace (iobenguane I 131)
Intervention Description
Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic dose
Primary Outcome Measure Information:
Title
MTD of Ultratrace Iobenguane I 131
Description
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.
Time Frame
6 weeks post therapy dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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.
Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Molecular Insight Pharmaceuticals
Organizational Affiliation
MIP
Official's Role
Study Director
Facility Information:
Facility Name
New York Presbyterian Hospital-Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29099942
Citation
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.
Results Reference
derived
Learn more about this trial
Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma
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