A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors

This study has been completed.
Sponsor:
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01413503
First received: August 8, 2011
Last updated: August 12, 2011
Last verified: August 2011
  Purpose

This is an ongoing prospective Phase II clinical trial evaluating the efficacy of 131I-MIBG for the treatment of patients with metastatic or unresectable pheochromocytoma and related tumors.


Condition Intervention Phase
Pheochromocytoma
Paraganglioma
Radiation: 131I-MIBG
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of 131I-labeled Metaiodobenzylguanidine (MIBG) for Treatment of Patients With Metastatic or Unresectable Pheochromocytoma and Related Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Post 131I-MIBG Evaluation [ Time Frame: 3 months after therapy ] [ Designated as safety issue: No ]
    Patients will be evaluated for disease response.


Enrollment: 50
Study Start Date: May 1991
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 131I-MIBG Radiation: 131I-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 1200 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: MIBG

Detailed Description:
  1. To assess the efficacy of high-dose 131I-MIBG in the treatment of patients with malignant pheochromocytoma and related tumors, with the basis of this initial examination being the percentage of patients in CR or PR, and the percentage of patients without PD for 3 years after the initial administration on 131I-MIBG therapy.
  2. To describe the response rate of malignant pheochromocytoma patients treated with high-dose 131I-MIBG.
  3. To describe the toxicity of high-dose 131I-MIBG in patients with malignant pheochromocytoma.
  4. To describe the overall survival and failure-free survival of malignant pheochromocytoma patients treated with high-dose 131I-MIBG.
  5. To determine the utility of using the serum level of Chromogranin A as a tumor marker for patients with malignant pheochromocytoma.
  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic Documentation: Histologic documentation of malignant pheochromocytoma or related tumors (paraganglioma, neuroblastoma, medullary thyroid carcinoma, carcinoid tumors), not amenable to curative surgery. Any site of origin of malignant pheochromocytoma, including but not limited to: adrenal, neck, thorax, abdominal, or pelvis is allowed.
  • Prior Treatment:

    • No cytotoxic chemotherapy for at least 3 weeks prior to high-dose 131I-MIBG or concurrent with high-dose 131I-MIBG.
    • > 2 weeks since major surgery.
    • > 4 weeks since completion of prior radiation therapy, as long as measurable disease lies outside the radiation port.
    • No treatment with an investigational agent concurrent or within 30 days of high-dose 131I-MIBG.
    • Patients who have received previous chemotherapy or radiation therapy must have evidence of persistent disease on 123I-MIBG scan and elevated tumor markers or measurable CT lesions before receiving high-dose 131I-MIBG.
  • Metastases Excluding Eligibility: No patients with a known significant MIBG-avid parenchymal brain metastasis; leptomeningeal metastases do not exclude eligibility. Hepatic metastases exclude eligibility if they functionally impair liver function (AST or total bilirubin ≥ 2.5 times the ULN).
  • Measurable Disease Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 10 mm as measured with CT scanning. Lesions < 10 mm diameter or bone lesions in the presence of demonstrable uptake of 123I-MIBG on diagnostic scanning, plus elevated levels of tumor markers that are specific for malignant pheochromocytoma: plasma catecholamines or metanephrines, urine catecholamines or metanephrines, serum chromogranin A. Lesions whose size is considered non-measurable include the following:

    • Bone lesions (see above)
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Chylothorax
    • Lesions within the chest or abdomen that are not confirmed to be pheochromocytoma by biopsy or 123I-MIBG scanning.
  • 131I-MIBG or 123I-MIBG Avidity: All patients must have 123I-MIBG or 131I-MIBG whole-body scanning prior to therapy. Metastases must be avid for the isotope such that their measured gamma radiation measures ≥ twice that of background radiation.
  • Subsequent 131I-MIBG Therapies: Patients must have had pain relief or a SD or PR after a prior therapy to be eligible for another therapy. Patients with PD within 9 months of the prior therapy are excluded from receiving subsequent therapy.
  • Age: ≥4 years of age.
  • Life Expectancy: greater than 9 months.
  • Karnofsky Performance Status: 70% or higher.
  • Anticoagulation: Heparin, LMW heparin, coumadin, and other anticoagulants may be used only when platelet counts are ≥ 100,000/micronL. Platelet counts will be monitored twice weekly after 131I-MIBG therapy.
  • Pregnancy & Nursing: Non-pregnant and non-nursing because the effects of high-dose 131I-MIBG on the fetus/infant are unknown.
  • Second Malignancies:

    • Patients with a "currently active" second malignancy, other than non-melanoma skin cancers, are not eligible.
    • Patients are not considered to have a "currently active" second malignancy if they have been cancer-free for ≥5 years.
  • Intercurrent Illness: No patients with uncontrolled intercurrent illness including but not limited to: ongoing active infections, grade 3 or 4 congestive heart failure by echocardiogram, nephrotic syndrome, serum albumin < 3, significant ascites or pleural effusion, pulmonary function testing (FVC) less than 70% of predicted for age, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Required Initial Laboratory Data (Minimum Levels):

    • Neutrophil count >/= 1,000/micronL
    • Platelet count >/= 80,000/micronL
    • AST (SGOT) ≤ 2.5 x ULN
    • Total bilirubin ≤ 2.5 x ULN
    • Creatinine ≤ 2 x ULN

Exclusion Criteria:

  • 1) Pregnancy & Nursing: Non-pregnant and non-nursing because the effects of high-dose 131I-MIBG on the fetus/infant are unknown.
  • 2) Second Malignancies:

    • Patients with a "currently active" second malignancy, other than non-melanoma skin cancers, are not eligible.
    • Patients are not considered to have a "currently active" second malignancy if they have been cancer-free for ≥5 years
  • 3) Intercurrent Illness: No patients with uncontrolled intercurrent illness including but not limited to: ongoing active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  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: NCT01413503

Locations
United States, California
UCSF
San Francisco, California, United States, 94103
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Paul Fitzgerald UCSF School of Medicine
  More Information

No publications provided

Responsible Party: Katherine Matthay, UCSF School of Medicine
ClinicalTrials.gov Identifier: NCT01413503     History of Changes
Other Study ID Numbers: Phase II Pheo
Study First Received: August 8, 2011
Last Updated: August 12, 2011
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 28, 2014