Compassionate Use of 131I-MIBG for Patients With Malignant Pheochromocytoma

Expanded access is currently available for this treatment.
(Study has been suspended after the event of an serious adverse event.)
Verified September 2013 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01377532
First received: June 13, 2011
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

This is a compassionate use protocol to allow palliative therapy for patients with malignant pheochromocytoma and paragangliomas.


Condition Intervention
Pheochromocytoma
Paraganglioma
Drug: 131 I-Metaiodobenzylguanidine (131 I-MIBG)

Study Type: Expanded Access     What is Expanded Access?
Official Title: Compassionate Use of 131I-MIBG for Patients With Malignant Pheochromocytoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Study Start Date: August 2009
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 131 I-Metaiodobenzylguanidine (131 I-MIBG)
    Therapeutic 131I-MIBG will be synthesized at Nuclear Diagnostic Products (NDP; Rockaway, New Jersey) with specific activities of 9-18 Ci/mmole. The therapeutic dose: 8-12 mCi/kg (maximum 500 mCi ± 10% at investigator's discretion) will be diluted in 25 ml of normal saline, and will be infused intravenously through a patient's peripheral or central line over 120 minutes. The patient will remain in a radiation protected isolation room until radiation emissions are ≤ 2 mr/hr at a 1 meter distance or meets institutional and state guidelines. This usually takes 4-6 days. In all cases, special shielding will be equipped in the room to minimize exposure to the outside environment and personnel will observe institutional radiation safety precautions.
    Other Name: 131I-MIBG
Detailed Description:

Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare tumors, with an incidence of 2-8 cases per million annually. These tumors develop in both children and adults. About 15-20% metastasize. Chemotherapy for this tumor usually consists of a combination of cyclophosphamide, vincristine, and dacarbazine delivered over two days and repeated every 3 weeks. Such combined chemotherapy is ineffective for the majority of patients with metastatic PHEO/PGL. A few patients with malignant PHEO have experienced remissions with sunitinib, but the drug may produce severe toxicity and the experience with that drug is limited. Those patients who do experience a remission with chemotherapy must continue it indefinitely to stay in remission. However, most such patients experience such severe side effects from the chemotherapy (marrow suppression, neuropathy, etc) that their chemotherapy must be discontinued. Thus, chemotherapy is either ineffective or intolerable for the vast majority of patients with metastatic PHEO/PGL.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis: Refractory or relapsed PHEO/PGL with original diagnosis based on tumor histopathology or the finding of PHEO/PGL tumor cells in the bone marrow. The diagnosis may also be based upon the presence of high plasma fractionated metanephrines or high urine catecholamines/metanephrines with diagnostic MIBG uptake.
  • Age: > 2 years and able to cooperate with radiation safety restrictions during therapy period.
  • Disease status: It must be determined that either the PHEO/PGL tumors are not amenable to safe surgical resection or are metastatic. Disease evaluable by MIBG scan must be present within 6 weeks of study entry and subsequent to any intervening therapy.
  • Life Expectancy: greater than 3 months.
  • Lanksy and Karnofsky Performance Status: 70% or higher.
  • Prior Therapy: Patients may enter this study with or without having had other therapy for recurrent tumor. Patients may be treated who have not had chemotherapy or radiation therapy. Patients may also be treated who have failed to respond to standard chemotherapy or radiation therapy. Patients must have fully recovered from the toxic effects of any prior therapy. At least 2 weeks should have elapsed since any anti-tumor therapy and the patient must meet hematologic criteria below. Three months should have elapsed in the case of completing radiation to any of the following fields: total craniospinal, total abdominal, whole lung, total body irradiation). Cytokine therapy (eg G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued a minimum of 24 hours prior to MIBG therapy. Prior 131I-MIBG therapy is allowed if > 8 weeks from previous treatment. Cumulative lifetime dose of 131I-MIBG, including the planned treatment, should not exceed 36 mCi/kg.
  • Liver function: bilirubin < 2x upper limit of normal (ULN). Exception: Gilbert syndrome); AST < 10x ULN.
  • Kidney function: Creatinine =< 2x ULN.
  • Hematopoietic Criteria Patients must have adequate hematopoietic function (without transfusion): ANC >750 x 10E9/L; Platelets >50 x 10E9/L if stem cells are not available; if stem cells are available, the patient should be independent of platelet transfusions with a platelet count of at least 20 x 10E9/L. Hemoglobin >10g/dl at time of treatment (transfusion allowed). Patients with granulocytopenia and/or thrombocytopenia due to tumor metastatic to the bone marrow may be eligible after discussion with Dr. Fitzgerald or designee.
  • Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no oxygen requirement.
  • No clinically significant cardiac dysfunction, normal EKG and EJ >50%

Exclusion Criteria:

  • Patients with disease of any major organ system that would compromise their ability to withstand therapy. Any significant organ impairment should be discussed with the Study Chair or Vice Chair prior to patient entry.
  • Patients with proteinuria in the absence of urinary infection 4 weeks prior to the planned treatment date.
  • Because of the teratogenic potential of the study medications, no patients who are pregnant or breast feeding will be allowed. Patients of childbearing potential must practice an effective method of birth control while participating on this study, to avoid possible pregnancy.
  • Patients who are on hemodialysis.
  • Patients with active infections that meet grade 3-4 toxicity criteria.
  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: NCT01377532

Contacts
Contact: Paul Fitzgerald, MD 415 665 1136 Paul.Fitzgerald@ucsf.edu

Locations
United States, California
UCSF
San Francisco, California, United States, 94143
Principal Investigator: Paul Fitzgerald, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Paul Fitzgerald, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01377532     History of Changes
Other Study ID Numbers: CompUse MIBG Pheo
Study First Received: June 13, 2011
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Pheochromocytoma
Paraganglioma
MIBG
131I-MIBG
Resistant
Relapsed
Treatment
UCSF
Pediatric
Adult
Oncology

Additional relevant MeSH terms:
Paraganglioma
Pheochromocytoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
3-Iodobenzylguanidine
Antineoplastic Agents
Diagnostic Uses of Chemicals
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiopharmaceuticals
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014