A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors
Condition: Pheochromocytoma; Paraganglioma
MeSH terms: Pheochromocytoma; Paraganglioma
Intervention: 131I-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.
Intervention MeSH terms: 3-Iodobenzylguanidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Pheochromocytoma; Paraganglioma; MIBG; 131I-MIBG; Resistant; Relapsed; Treatment; UCSF; Pediatric; Adult; Oncology

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.
    

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.