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

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.

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.