Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03649438
Recruitment Status : Not yet recruiting
First Posted : August 28, 2018
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Tanya Watt, University of Texas Southwestern Medical Center

Brief Summary:
This expanded access is the best available therapy/compassionate use designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with relapsed/refractory neuroblastoma or 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.

Condition or disease Intervention/treatment Phase
Relapsed Neuroblastoma Metastatic Pheochromocytoma Drug: 131 I-Metaiodobenzylguanidine Drug: Potassium Iodide Drug: G-csf Early Phase 1

Detailed Description:

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

Secondary Objectives are to (1) assess disease response to 131I-MIBG therapy for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma; (2) gain more information about the toxicities of 131I-MIBG therapy; and (3) assess improvement of symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG therapy.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: 131 I-MIBG Treatment Arm
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.
Drug: 131 I-Metaiodobenzylguanidine
  • 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.
  • Dose of 12 mCi/kg for patients without a stem cell source with normal renal function and meets other eligibility criteria.
  • Dose of > 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients meeting eligibility criteria with stem cells available.
Other Name: 131I-MIBG

Drug: Potassium Iodide
For the therapeutic MIBG administration, potassium iodide solution will be administered in a loading dose of 6mg/kg orally at least 8 hours prior to the MIBG injection, and then will be given at 1mg/kg/dose every 4 hours on days 0-6, then 1 mg/kg/day through day 45 post injection.
Other Name: KI solution

Drug: G-csf
It is recommended that patients with ANC less than 750 after MIBG infusion begin G-CSF 5 mcg/kg/day subcutaneously (or receive equivalent single dose of Neulasta every 14 days while neutropenic) until neutrophil recovery (generally >5000). This will start 24 hours after stem cell infusion (if stem cells are to be infused).
Other Name: Neulasta




Primary Outcome Measures :
  1. Number of patients who receive 131 I-MIBG [ Time Frame: 2 hours ]
    The number of patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who receive access to 131I-MIBG therapy.


Secondary Outcome Measures :
  1. Disease Outcome [ Time Frame: Until 1 year post therapy or completion of the study ]
    Disease response to 131I-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 Curie Score and RECIST criteria for patients who have measurable 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 therapy or initiation of another therapy.

  2. Incidence of hematologic toxicities [ Time Frame: Until 1 year post therapy or completion of the study ]
    Evaluation of hematologic toxicities of 131I MIBG therapy. Complete Blood Count (CBC) with differential and platelet count will be obtained prior to study enrollment, on day 0 and then twice weekly until Absolute Neutrophil Count (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.

  3. Incidence of hepatic toxicities [ Time Frame: Until 1 year post therapy or completion of the study ]
    Alanine Aminotransferase (ALT), Aspartate Aminotransferase (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.

  4. Incidence of thyroid toxicities [ Time Frame: Until 1 year post therapy or completion of the study ]
    Thyroxine (T4) and Thyroid Stimulating Hormone (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.

  5. Improvement of pain symptoms [ Time Frame: Day of MIBG therapy (day 0), day 7; Weekly until Day 42; Day 56 ]
    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.

  6. Improvement of fatigue [ Time Frame: Day of MIBG therapy (day 0), day 7; Weekly until Day 42; Day 56 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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: patients must have a life expectancy of at least 8 weeks
  • Disease status: Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any phase of standard therapy (any new lesion or an increase in size >25% of a pre-existing lesion). Patients may enter this study with or without re-induction therapy for recurrent tumor.
  • 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: If a patient does not have a hematopoietic stem cell product available for re-infusion after MIBG treatment, they may not receive a 131IMIBG dose >12 mCi/kg. Patients must have a hematopoietic stem cell product available for re-infusion after MIBG treatment at doses of > 12 mCi/kg. The minimum quantity for peripheral blood stem cells is 1.5 x 106 CD34+ cells/kg (optimum > 2 x 106 CD34+ cells/kg). The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum >2.0 x 108 mononuclear cells/kg).
  • Stem cell source: The patients on this protocol will have autologous PBSCs available.
  • Have acceptable organ function as defined below within 7 days of enrollment:
  • Bone Marrow: ANC ≥750 X 109 /L, platelets ≥50,000 X 109 /L, and hemoglobin ≥ 8.0 g/dL without transfusion if stem cells are not available. ANC ≥500 X 109 /L, platelets ≥20,000 X 109 /L, and hemoglobin ≥ 8.0 g/dL with transfusions allowed if stem cells are available. Patients with stem cells available are excluded if they require two platelet transfusions per week to maintain the minimum required platelet count. A bone marrow examination is not medically indicated for patients diagnosed with metastatic pheochromocytoma.
  • Renal: Creatinine ≤ 2 times upper limit of normal
  • Hepatic: Bilirubin ≤2x upper limit of normal; AST/ALT ≤10x upper limit of normal
  • Cardiac: Ejection fraction ≥ 45% on echocardiogram or shortening fraction

    >/=27%

  • Pulmonary: normal lung function as manifested by no dyspnea and/or oxygen saturation ≥ 94% on room air.
  • Prior Therapy: Patients must have recovered from all acute toxicities (defined as CTCAE 5.0 ≤ 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 elapsed.
  • 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 must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

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
  • Patients who have had prior treatment with 131I-MIBG who do not meet the re-treatment criteria.
  • In patients with metastatic pheochromocytoma, screening urinalysis required prior to study enrollment. If random collection urine specimen is positive for proteinuria, patients must have 24-hour urine protein determination. Patients with metastatic pheochromocytoma are excluded if 24-hour urine protein is above the institutional upper limit of normal.
  • Patients with known MIBG-avid parenchymal brain metastases are excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649438


Contacts
Layout table for location contacts
Contact: Tanya Watt, MD 214-456-6363 Tanya.Watt@UTSouthwestern.edu

Locations
Layout table for location information
United States, Texas
The University of Texas Southwestern Medical Center Not yet recruiting
Dallas, Texas, United States, 75235
Contact: Tanya Watt, MD    214-456-6363    Tanya.Watt@UTSouthwestern.edu   
Principal Investigator: Tanya Watt, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Tanya Watt, MD University of Texas Southwestern Medical Center

Layout table for additonal information
Responsible Party: Tanya Watt, Assistant Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03649438     History of Changes
Other Study ID Numbers: STU 052018-010
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroblastoma
3-Iodobenzylguanidine
Pheochromocytoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Paraganglioma
Neuroendocrine Tumors
Iodine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs