Description:
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.
Title
- Brief Title: MIBG for Refractory Neuroblastoma and Pheochromocytoma
- Official Title: 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Refractory Neuroblastoma and Pheochromocytoma
Clinical Trial IDs
- ORG STUDY ID:
2012LS107
- NCT ID:
NCT01850888
Conditions
- Relapsed Neuroblastoma
- Metastatic Pheochromocytoma
Interventions
Drug | Synonyms | Arms |
---|
131 I-Metaiodobenzylguanidine (131I-MIBG) | 131I-MIBG | 131 I-MIBG Treatment Arm |
Potassium iodide solution | KI solution | 131 I-MIBG Treatment Arm |
G-CSF | Neulasta | 131 I-MIBG Treatment Arm |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
131 I-MIBG Treatment Arm | Experimental | Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria. | - 131 I-Metaiodobenzylguanidine (131I-MIBG)
- Potassium iodide solution
- G-CSF
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 1 Year |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients who receive 131 I-MIBG. |
Time Frame: | 2 hours |
Safety Issue: | |
Description: | The number of patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who receive access to 131 I-MIBG. |
Secondary Outcome Measures
Measure: | Disease response |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Disease response to 131 I-MIBG therapy in patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma. Disease response will be measured by Curie Score for patients with MIBG avid disease only or by both Currie Score and RECIST criteria for patients who have measureable disease in addition to MIBG avid disease. Disease response will be assessed at day 56 (+/- 14 days) and then every 3 months until 1-year post treatment, then every 6 months until progression, death or other therapy. |
Measure: | Incidence of hematologic toxicities |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Evaluation of hematologic toxicities of 131I MIBG therapy. CBC with differential and platelet count will be obtained prior to study enrollment, on day 0 and then twice weekly until ANC>500/mm3 and platelet count >20,000 x 3 days without transfusion. Once that is achieved CBC will be then obtained on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy. In addition, we will be looking at the percent of patient that require infusion of stem cell product for cytopenias. |
Measure: | Incidence of hepatic toxicities |
Time Frame: | 1 year |
Safety Issue: | |
Description: | ALT, AST, bilirubin will be obtained prior to study enrollment and then weekly until day 42, again on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy |
Measure: | Incidence of Thyroid Toxicity |
Time Frame: | 1 year |
Safety Issue: | |
Description: | T4 and TSH will be obtained prior to study enrollment and again on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy. |
Measure: | Improvement of pain symptoms |
Time Frame: | 56 days |
Safety Issue: | |
Description: | Assessment of pain will occur on day 0 of therapy, on the day of discharge and then weekly until day 42 and then again on day 56. The PedsQL Pediatric Pain Questionnaire will be used for assessment of pain in all patients. These questionnaires include both patient report and parent report, when appropriate. |
Measure: | Improvement of fatigue |
Time Frame: | 56 days |
Safety Issue: | |
Description: | Assessment of fatigue will occur on day 0 of therapy, on the day of discharge and then weekly until day 42 and then again on day 56. The PedsQL Multidimensional Fatigue Scale will be used for assessment of fatigue in all patients. These scales include both patient report and parent report, when appropriate. |
Details
Phase: | N/A |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Masonic Cancer Center, University of Minnesota |
Trial Keywords
- neuroblastoma
- pheochromocytoma
Last Updated
January 22, 2021