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

Primary Purpose

Pheochromocytoma, Paraganglioma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
131I-MIBG
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pheochromocytoma focused on measuring Pheochromocytoma, Paraganglioma, MIBG, 131I-MIBG, Resistant, Relapsed, Treatment, UCSF, Pediatric, Adult, Oncology

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCSF

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

131I-MIBG

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Patients With Complete (CR), Partial (PR), or Minor (MR) Response and Without Progressive Disease
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.

Secondary Outcome Measures

Full Information

First Posted
August 8, 2011
Last Updated
December 23, 2017
Sponsor
University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT01413503
Brief Title
A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors
Official Title
A Phase II Study of 131I-labeled Metaiodobenzylguanidine (MIBG) for Treatment of Patients With Metastatic or Unresectable Pheochromocytoma and Related Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
May 1991 (undefined)
Primary Completion Date
September 6, 2007 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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. To describe the response rate of malignant pheochromocytoma patients treated with high-dose 131I-MIBG. To describe the toxicity of high-dose 131I-MIBG in patients with malignant pheochromocytoma. To describe the overall survival and failure-free survival of malignant pheochromocytoma patients treated with high-dose 131I-MIBG. To determine the utility of using the serum level of Chromogranin A as a tumor marker for patients with malignant pheochromocytoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pheochromocytoma, Paraganglioma
Keywords
Pheochromocytoma, Paraganglioma, MIBG, 131I-MIBG, Resistant, Relapsed, Treatment, UCSF, Pediatric, Adult, Oncology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
131I-MIBG
Arm Type
Experimental
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
131I-MIBG
Other Intervention Name(s)
MIBG
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Patients With Complete (CR), Partial (PR), or Minor (MR) Response and Without Progressive Disease
Description
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.
Time Frame
After 1 year from initial treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Fitzgerald
Organizational Affiliation
UCSF School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19636009
Citation
Gonias S, Goldsby R, Matthay KK, Hawkins R, Price D, Huberty J, Damon L, Linker C, Sznewajs A, Shiboski S, Fitzgerald P. Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol. 2009 Sep 1;27(25):4162-8. doi: 10.1200/JCO.2008.21.3496. Epub 2009 Jul 27.
Results Reference
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A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors

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