Clinical Trials /

MIBG for Refractory Neuroblastoma and Pheochromocytoma

NCT01850888

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.

Related Conditions:
  • Adrenal Gland Pheochromocytoma
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

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

DrugSynonymsArms
131 I-Metaiodobenzylguanidine (131I-MIBG)131I-MIBG131 I-MIBG Treatment Arm
Potassium iodide solutionKI solution131 I-MIBG Treatment Arm
G-CSFNeulasta131 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

NameTypeDescriptionInterventions
131 I-MIBG Treatment ArmExperimentalTherapeutic 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