Clinical trial NCT01850888: MIBG for Refractory Neuroblastoma and Pheochromocytoma
Official title: 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Refractory Neuroblastoma and Pheochromocytoma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Relapsed Neuroblastoma
Metastatic Pheochromocytoma
Keywords: neuroblastoma
pheochromocytoma
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2013-05-10
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a best available therapy/compassionate use single institution study designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with progressive neuroblastoma and metastatic pheochromocytoma who are not eligible for therapies of higher priority. Patients may receive a range of doses depending on stem cell availability and tumor involvement of bone marrow. Response rate, toxicity, and time to progression and death will be evaluated.

Detailed description: Primary Objective is to provide access to therapy with 131I-MIBG for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Secondary Objective is to assess disease response to 131I-MIBG therapy for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Tertiary Objectives are to 1) gain more information about the toxicities of 131I-MIBG therapy; 2) assess improvement of symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG therapy.

* The therapeutic dose of 131I-MIBG will be based on the following:

  1. Minimum dose of 10 mCi/kg for patients without a stem cell source whose renal function is above the upper limit of normal but still meets eligibility criteria.
  2. Dose of 12 mCi/kg for patients without a stem cell source with normal renal function and meets other eligibility criteria.
  3. Dose of \> 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients meeting eligibility criteria with stem cells available.
* A urinary catheter and intravenous fluids will be used for bladder protection, and potassium iodide solution for thyroid Protection.
* G-CSF is recommended for patients with ANC less than 750 after MIBG infusion.
* hematopoietic stem cell infusion is recommended for patients with grade 4 hematologic toxicity following 131I-MIBG therapy that continues to have an ANC \<200 on G-CSF without signs of recovery for \>2 weeks and any patient requiring platelet transfusion more than two times weekly for 4 consecutive weeks.
* Follow-up will be done until disease progression, death or other therapies are initiated.

Eligibility criteria: Inclusion Criteria:

* Diagnosis:

  * Relapsed/refractory neuroblastoma with original diagnosis based on tumor histopathology or elevated urine catecholamines with typical neuroblastoma cells in the bone marrow
  * Metastatic pheochromocytoma
* Age \>1 year and able to cooperate with radiation safety restrictions during therapy period
* Karnofsky or Lansky performance status of ≥ 50%
* Life expectancy: ≥ at least 8 weeks
* Disease status: Failure to respond to standard therapy or development of progressive disease at any time.
* Disease must be evaluable by MIBG scan. A positive MIBG scan must be present within 8 weeks prior to study entry and subsequent to any intervening therapy. If the patient has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done at least 4 weeks after radiation was completed and must show viable neuroblastoma.
* Stem Cells: Patients must have a hematopoietic stem cell product available for reinfusion after MIBG treatment at doses of \> 12 mCi/kg.
* Have acceptable organ function as defined below within 7 days of enrollment:

  * Bone Marrow: ANC ≥750 X 109 /L and platelets ≥50,000 X 109 /L without transfusion if stem cells are not available (any ANC or platelet allowed if stem cells available)
  * Renal: Creatinine ≤3x upper limit of normal
  * Hepatic: Bilirubin ≤2x upper limit of normal; AST/ALT ≤10x upper limit of normal
  * Cardiac: Ejection fraction ≥45% on echocardiogram
  * Pulmonary: normal lung function as manifested by no dyspnea and/or oxygen saturation ≥ 88% on room air.
* Prior Therapy: Patients must have recovered from all acute toxicities (defined as CTCAE 4.0 ≤ grade 1) associated with any prior therapy, and:

  * Myelosuppressive chemotherapy: At least 2 weeks should have elapsed since any chemotherapy causing myelosuppression
  * Biologic (anti-neoplastic agent): At least 7 days should have elapsed since the completion of therapy with a biologic agent.
  * Monoclonal antibodies: At least 3 half-lives should have elapsed since therapy with a monoclonal antibody
  * Radiation therapy: 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). For all other sites of radiation, at least 2 weeks should have relapsed.
  * Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, IL-2): must be discontinued a minimum of 24 hours prior to MIBG therapy.
* Voluntary written informed consent

Exclusion Criteria:

* Patients with disease of any major organ system that would compromise their ability to withstand therapy.
* Because of the teratogenic potential of the study medication, 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.
* Known allergy to any of the agents or their ingredients used in this study.
* Patients who are on hemodialysis
* Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies

Primary outcomes:
measure: Number of patients who receive 131 I-MIBG.
timeFrame: 2 hours
Secondary outcomes:
measure: Disease response
timeFrame: 1 year
measure: Incidence of hematologic toxicities
timeFrame: 1 year
measure: Incidence of hepatic toxicities
timeFrame: 1 year
measure: Incidence of Thyroid Toxicity
timeFrame: 1 year
measure: Improvement of pain symptoms
timeFrame: 56 days
measure: Improvement of fatigue
timeFrame: 56 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
Study officials:
affiliation: University of Minnesota Department of Pediatrics
name: Emily Greengard, MD
role: PRINCIPAL_INVESTIGATOR
References: