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An Open Label, Expanded Access Protocol Using 131I-metaiodobenzylguanidine (131I-MIBG)Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma

12 Months
Open (Enrolling)
Neuroblastoma, Pheochromocytoma, Paraganglioma

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Trial Information

An Open Label, Expanded Access Protocol Using 131I-metaiodobenzylguanidine (131I-MIBG)Therapy in Patients With Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma

Neuroblastoma, pheochromocytoma, and paraganglioma remain fatal diseases for a large
percentage of patients, especially those with high-risk disease features who become
resistant to conventional therapy. 131I-metaiodobenzylguanidine (131I-MIBG) is a
norepinephrine analog that concentrates in adrenergic tissue and has been shown to be
sensitive and specific for detecting localized and metastatic neuroblastoma,
pheochromocytoma, and paraganglioma. More importantly, experience of many institutions has
proven that this agent used as a targeted radiotherapeutic has significant anti-tumor
activity against refractory neuroblastoma 1-7 as well as pheochromocytoma and paraganglioma.
Children's Hospital of Philadelphia, UCSF, and the University of Michigan have just
completed a large Phase 2 study of 131I-MIBG given in doses of 10-18 mCi/kg with stem cell
rescue, if necessary, and have shown that this agent is safe and effective palliative
therapy for refractory or relapsed neuroblastoma patients. In addition, there is growing
evidence that low-dose (5-10 mCi/kg) submyeloablative MIBG therapy is both safe and
effective for disease palliation. This protocol therefore provides a mechanism to deliver
this therapy when clinically indicated.

Inclusion Criteria:

- Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on
tumor histopathology or elevated urine catecholamines with typical tumor cells in the
bone marrow, OR pheochromocytoma or paraganglioma not amenable to curative surgery

- Age ≥ 12 months and able to cooperate with radiation safety restrictions during
therapy period with/without pharmacologic anxiolysis.

- Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any time (any new lesion or an increase in size of > 25% of a pre-existing
lesion). Disease evaluation must be completed within 8 weeks of study entry. If
possible, the disease evaluation should take place subsequent to any intervening
therapy; if intervening therapy does occur, evaluations should be done as clinically
indicated. If patient has received prior treatment with MIBG, they must have a
response or stable disease after the most recent MIBG infusion. Patient may have PD
after showing an initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).

- Stem cells: Patients must have a hematopoietic stem cell product available for
re-infusion after 131I-MIBG treatment at doses of ≥ 12 mCi/kg. If no stem cells are
available, then the dose of 131I-MIBG should be < 12 mCi/kg.

- The minimum quantity for purged or unpurged peripheral blood stem cells (PBSC)
is 1.5 x 106 viable CD34+ cells/kg (recommended 2 x 106 viable CD34+ cells/kg).

- The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum >
2.0 x 108 mononuclear cells/kg).

- Prior Therapy: Patients may enter this study with or without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy, meeting the following criteria: At least 2 weeks should have elapsed
since any anti-tumor therapy and the patient must meet hematologic criteria below.
Three-months should have elapsed in the case of completing radiation to any of the
following fields: craniospinal, total abdominal, whole lung, total body irradiation
(spot irradiation to skull-based metastases is NOT considered craniospinal radiation
for the purposes of this study. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6,
erythropoietin) must be discontinued a minimum of 24 hours prior to 131I-MIBG

- Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit of

- Kidney function: Serum Creatinine ≤ 2x upper limit of normal OR 24-hr creatinine
clearance OR GFR ≥ 60 ml/min/1.73m2(For example, a patient would meet this criteria
if GFR < 60 ml/min/1.73m2 but serum creatinine ≤ 2x upper limit of normal.)

- Hematologic Criteria: ANC ≥ 750/µL; Platelets ≥ 50,000/µL without transfusion if stem
cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells
available). Patient must be off myeloid growth factors for at least 24 hours. If the
patient has received prior treatment with MIBG, they may be thrombocytopenic, but
requiring no more than 2 platelet transfusions per week to maintain counts above
20,000. Hemoglobin must be ≥ 10 gm/dL (transfusion allowed) regardless of stored
stem cell availability.

- Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no
oxygen requirement

- No clinically significant cardiac dysfunction

- Signed informed consent/assent: The patient and/or the patient's legally authorized
guardian must acknowledge in writing that consent/assent to become a study subject
has been obtained, in accordance with institutional policies approved by the U.S.
Department of Health and Human Services.

Exclusion Criteria:

- Patients with disease of any major organ system that would compromise their ability
to withstand therapy. Any significant organ impairment should be discussed with the
Principal Investigator prior to patient entry.

- Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential must
practice an effective method of birth control while participating on this study, to
avoid possible damage to the fetus. Abstinence is an effective method of birth

- Patients who are on hemodialysis

- Proteinuria, in the absence of urinary infection, within 4 weeks prior to the planned
treatment date is a relative contraindication to receiving therapy for patients with
pheochromocytoma/paraganglioma. Patients with pheochromocytoma/paraganglioma with any
proteinuria must have a 24-hr urine protein determination. If proteinuria is
confirmed as being above the institutional upper limit of normal, the patient is
ineligible for MIBG therapy.

- Patients with active infections that meet grade 3-4 according to the NCI CTCAE v3.0.

- Patients with known MIBG-avid parenchymal brain metastases are not eligible.
(Patients with leptomeningeal or skull-based metastases are eligible.)

Type of Study:

Expanded Access

Study Design:


Principal Investigator

Weiss Brian, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cincinnati Children's Hospital (


United States: Food and Drug Administration

Study ID:




Start Date:

Completion Date:

Related Keywords:

  • Neuroblastoma
  • Pheochromocytoma
  • Paraganglioma
  • Neuroblastoma
  • Paraganglioma
  • Pheochromocytoma