PheochromocytomaPhase 2NCT01413503

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

A Phase 2 study testing 131I-MIBG in people with Pheochromocytoma and Paraganglioma, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 4 years and older
Conditions the study is for: Pheochromocytoma, Paraganglioma
What is being tested?: 131I-MIBG
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteUnited States
Study dates: May 1991to May 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 4 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Show all 32Show fewer

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

UCSF
San Francisco, California, 94103

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Pheochromocytoma, Paraganglioma
Being tested: 131I-MIBG
Keywords: Pheochromocytoma, Paraganglioma, MIBG, 131I-MIBG, Resistant, Relapsed, Treatment, UCSF, Pediatric, Adult, Oncology
Medical subject headings: Pheochromocytoma, Paraganglioma, Recurrence, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

131I-MIBGRadiation
Also called 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.

Study groups in NCT01413503
Study group	Role	What they receive
131I-MIBG	Experimental	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 Receives: Radiation: 131I-MIBG

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: After 1 year from initial treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 1991May 2009

First posted10 Aug 2011 (estimated)
Study startMay 1991
Primary completion6 Sep 2007
Study completionMay 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for PheochromocytomaStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01413503
Sponsor's protocol ID: 03991
Status last verified: Dec 2017
First submitted: 8 Aug 2011
Last updated: 18 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 19636009

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Natural History Study of Children and Adults With Medullary Thyroid Cancer
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RecruitingPhase 2
Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor

All Pheochromocytoma trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of 131I-labeled Metaiodobenzylguanidine (MIBG) for Treatment of Patients With Metastatic or Unresectable Pheochromocytoma and Related Tumors
ClinicalTrials.gov ID: NCT01413503
Acronym / sponsor ID: 03991
Conditions: Pheochromocytoma, Paraganglioma
Keywords: Pheochromocytoma, Paraganglioma, MIBG, 131I-MIBG, Resistant, Relapsed, Treatment, UCSF
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Study start: May 1991
Primary completion: 6 Sep 2007 (actual)
Study completion: May 2009 (actual)
First posted: 10 Aug 2011 (estimated)
Results: Posted 18 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
131I-MIBG	Experimental	Radiation: 131I-MIBGPatients 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

Who may qualify

Ages: 4 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (32 listed)

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:
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:
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.

Key exclusion criteria (5 listed)

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:
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
131I-MIBGAlso: MIBGTherapeutic 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.	Radiation	131I-MIBG

Primary outcome

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.

Results and safety

Results posted to the registry on 18 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
131I-MIBG	50	49

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

Time frame: After 1 year from initial treatment. Count of participants. Unit: Participants

Measure	131I-MIBG n = 49
Value	28

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
131I-MIBG	6 of 49 (12.2%)	43 of 49 (87.8%)	4 of 49

Limitations and caveats (from the sponsor): All study data were destroyed in a flood after study completion and prior to results posting in ClinicalTrials.gov. Partial Adverse Event information was derived from publication-PubMed ID: 19636009

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19636009Gonias 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.

Related trials for Pheochromocytoma

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paul Fitzgerald principal investigator

UCSF School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 131I-MIBG in people with Pheochromocytoma and Paraganglioma, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Complete (CR), Partial (PR), or Minor (MR) Response and Without Progressive Disease (time frame: After 1 year from initial treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01413503, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2018.