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Phase 1 Study of Iobenguane (MIBG) I 131 in Patients With Malignant Pheochromocytoma/Paraganglioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00458952
First received: April 9, 2007
Last updated: June 13, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to determine whether iobenguane I 131 is safe and effective in patients with malignant pheochromocytoma or paraganglioma.

Condition Intervention Phase
Pheochromocytoma
Paraganglioma
Drug: Ultratrace Iobenguane (MIBG) I 131
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Molecular Insight Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • MTD of Ultratrace Iobenguane I 131 [ Time Frame: 6 weeks post therapy dose ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 24
Study Start Date: April 2007
Study Completion Date: June 2011
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
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.
Drug: Ultratrace Iobenguane (MIBG) I 131
Phase I: Dose escalation protocol Phase II: Treatment schedule at therapeutic dose
Other Names:
  • Ultratrace Iobenguane I 131
  • Azedra Ultratrace (iobenguane I 131)

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458952

Locations
United States, New York
New York Presbyterian Hospital-Weill Cornell Medical Center
New York, New York, United States, 10021
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Molecular Insight Pharmaceuticals, Inc.
Investigators
Study Director: Molecular Insight Pharmaceuticals MIP
  More Information

Responsible Party: Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00458952     History of Changes
Other Study ID Numbers: MIP-IB12 
Study First Received: April 9, 2007
Results First Received: December 15, 2015
Last Updated: June 13, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Molecular Insight Pharmaceuticals, Inc.:
MIBG
iobenguane
iodine
I 131
radiotherapy
radiopharmaceutical
dosimetry
neuroendocrine tumor
Ultratrace
no carrier added
metaiodobenzyl-guanidine

Additional relevant MeSH terms:
Paraganglioma
Carotid Body Tumor
Paraganglioma, Extra-Adrenal
Pheochromocytoma
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

ClinicalTrials.gov processed this record on December 07, 2016