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

December 23, 2017 updated by: Paul Fitzgerald, University of California, San Francisco

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94103
        • UCSF

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 131I-MIBG
Patients received 131I-MIBG 8-12 mCi/kg (maximum 500 mCi ± 10% at investigator's discretion) diluted in 25 ml of normal saline. Patients were infused intravenously through a patient's peripheral or central line over 120 minutes
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 Names:
  • MIBG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Complete (CR), Partial (PR), or Minor (MR) Response and Without Progressive Disease
Time Frame: After 1 year from initial treatment
Patients with complete (CR), partial (PR), or minor (MR) response and without progressive disease 1 year from initial treatment, using RECIST RESPONSE CRITERIA for measurable soft tissue tumor: CR=No Tumor (Primary or metastatic); catacholamines, metanephrines and chromogranin A all normal. PR=Primary and all measurable sites decreased >50%; number of positive bone sites decreased by >50%; bone marrow tumor decreased by 50%. MR=No new lesions; >50% reduction of any measurable lesion (primary or metastases); <25% increase in any existing lesion.
After 1 year from initial treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: Paul Fitzgerald, UCSF School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1991

Primary Completion (Actual)

September 6, 2007

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

August 8, 2011

First Submitted That Met QC Criteria

August 8, 2011

First Posted (Estimate)

August 10, 2011

Study Record Updates

Last Update Posted (Actual)

September 18, 2018

Last Update Submitted That Met QC Criteria

December 23, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03991

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pheochromocytoma

Clinical Trials on 131I-MIBG

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Colombia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe