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

NCT01413503 | Completed Phase 2 Results DMC

• 1 other identifier: 03991
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Pheochromocytoma; Paraganglioma

Keywords

Pheochromocytoma; Paraganglioma; MIBG; 131I-MIBG; Resistant; Relapsed; Treatment; UCSF; Pediatric; Adult; Oncology

Outcome Measures

Primary Outcomes (1)

• 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.

  After 1 year from initial treatment

Study Arms (1)

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

Radiation: 131I-MIBG

Interventions

131I-MIBG RADIATION

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.

Also known as: MIBG

131I-MIBG

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \) 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, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF

San Francisco, California, 94103, United States

Location

Related Publications (1)

• 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.

  PMID: 19636009 RESULT

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Recurrence; Neoplasms

Interventions

3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Limitations and Caveats

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

Results Point of Contact

• Title: Paul A. Fitzgerald, MD
• Organization: University of California, San Francisco

Paul.Fitzgerald2@ucsf.edu

415-665-1136

Study Officials

• Paul Fitzgerald

  UCSF School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 10, 2011
• Study Start: May 1, 1991
• Primary Completion: September 6, 2007
• Study Completion: May 1, 2009
• Last Updated: September 18, 2018
• Results First Posted: September 18, 2018

Record last verified: 2017-12

Locations

US (1)