131-I-MIBG Therapy for Refractory Neuroblastoma and Metastatic Pheochromocytoma (CHP-830)

Expanded access is currently available for this treatment.
Verified January 2014 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
John Maris, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01163383
First received: July 13, 2010
Last updated: January 16, 2014
Last verified: January 2014

July 13, 2010
January 16, 2014
March 2005
July 2015   (final data collection date for primary outcome measure)
Not Provided
Number of Participants with Disease Response to 131-I-MIBG [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Will measure disease response after treatment with 131 I- MIBG with post therapy scan. Will record response to therapy data for each subject after therapy.
Complete list of historical versions of study NCT01163383 on ClinicalTrials.gov Archive Site
Not Provided
Number of Participants with Adverse events related to 131 I- MIBG therapy [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Will measure the number of participants with adverse events as a measure of safety and tolerability
Not Provided
Not Provided
 
131-I-MIBG Therapy for Refractory Neuroblastoma and Metastatic Pheochromocytoma
CHP-830 I-Metaiodobenzylguanidine (131 I-MIBG) Therapy for Refractory Neuroblastoma and Metastatic Pheochromocytoma (An Expanded Access Protocol)

Metaiodobenzylguanidine (MIBG) is a substance that is taken up by neuroblastoma or pheochromocytoma tumor cells. MIBG is combined with radioactive iodine (131 I)in the laboratory to form a radioactive compound 131 I-MIBG. This radioactive compound delivers radiation specifically to the cancer cells and causes them to die.

The purpose of this research protocol is to provides a mechanism to deliver MIBG therapy when clinically indicated, but also to provide a mechanism to continue to collect efficacy and toxicity data that will be provided

General Description of the Medication Being Used on the Study:

Metaiodobenzylguanidine (MIBG) is a substance that is taken up by neuroblastoma or pheochromocytoma tumor cells. MIBG is combined with radioactive iodine (131I) in the laboratory to form the radioactive compound 131I-MIBG. The 131I-MIBG compound delivers radiation specifically to the neuroblastoma cancer cells and causes them to die. 131I-MIBG is experimental, but has been used in more than 100 children in the United States by itself to treat relapsed neuroblastoma and metastatic pheochromocytoma. A recent study using increasing doses of 131I-MIBG in both children and adults with relapsed neuroblastoma or metastatic pheochromocytoma showed anti-cancer effects in some of these patients. The main side effect of this treatment was a decrease in the number of normal blood-forming cells (called stem cells) in the bone marrow, but a dose of 12 mCi/kg did not cause permanent damage to the bone marrow in a small number of patients.

There are certain tests or procedures that will need to be done to confirm that the subject is eligible for this therapy. These include lab work, physical exam and MIBG scan. A CT scan, an MRI, a bone scan, Bone marrow aspirate and biopsy and urine tests will be done to evaluate your disease status when clinically indicated. Your doctor will determine which tests are required.

Before your child can begin treatment on this study, s/he will need to have an intravenous catheter (tube) placed in a vein. We can use an existing central venous catheter to administer the medicine.

Because your child's urine will be radioactive, a urinary catheter may be inserted through your child's urethra into the bladder to ensure drainage of the urine, which will be radioactive. The catheter will be removed 3-5 days following the treatment. General anesthesia or sedation is typically given for the procedure of inserting the catheter.

  1. Your child will be treated in a specially prepared room in the CHOP Pediatric Oncology Unit. Upon admission, the nursing staff will instruct you on the care you will give your child following the MIBG infusion. Because of the frequent exposure of the nursing staff to radiation and the high level of radiation surrounding your child during therapy, the nurses' contact will be limited to complex medical care, so that they are available for your child in the event of an emergency. Adult family members will be expected to be present at all times during the hospitalization to:

    • Assist with hygiene
    • Give oral medications
    • Offer and empty bedpans
    • Assist with meals
    • Change diapers (if used)
    • Change clothing and bed linens if soiled
    • Entertain or distract individuals who become upset or restless due to the isolation or procedures.
    • Record Dosimeter readings.
  2. Isolation: For 2-5 days your child will be placed in a single room with a bed surrounded by lead shielding to prevent exposure of visitors and hospital personnel to radioactivity. Family members may visit in the room, but must wear a radiation badge to measure exposure. A single family member can sleep in the room, but no one is allowed to go behind the shields or sleep in the bed with the child.
  3. Your child will receive fluids through the central venous catheter. The fluids will begin at least four hours before and continue at least 72 hours after the 131I-MIBG treatment begins.
  4. Your child will take a medicine by mouth, potassium iodide, to prevent thyroid damage from the radioactive iodine contained in the 131I-MIBG. This medication will be taken on the day of the treatment and will continue for a total of 6 weeks.
  5. The 131I-MIBG will be given through an intravenous catheter over 1.0 - 2-hours.
  6. During the administration of the drug, your child's blood pressure and heart rate will be checked frequently.
  7. Before and at regular intervals after treatment, your child will have routine blood tests to check his/her blood counts, hormone, liver and kidney functions. Blood will be checked at least weekly or more (if indicated) for approximately 6 weeks after the treatment. Approximately 1 teaspoon of blood will be drawn weekly for 6 weeks to perform the tests listed above.
  8. A MIBG scan will be performed to see where the drug is concentrating in the body following treatment. No injection of a radioactive marker will be required and this is usually done on the day for discharge. It is identical to the pretherapy MIBG scan except for not needing MIBG injection and it is usually shorter (15-30 minutes).
  9. Six to eight weeks after treatment, an MIBG and other scans will be done to evaluate the response of the tumor to the treatment.
  10. If your child's tumor is responding or stable 6-7 weeks after each treatment, s/he may be eligible for a second and third course of treatment, as long as his/her white blood counts have recovered from the treatment and the patient has stem cells available if needed. If another MIBG treatment is given, it will be at the same dose as the first treatment, unless it is thought to be necessary for safety reasons (based on toxicity information from the first infusion) to decrease the dose.
  11. If your child's blood counts decrease following the therapy, we will start Filgrastim (G-CSF) or Neulasta. G-CSF/neulasta is a medicine that helps increase the white blood cells. This is given by a subcutaneous (under the skin) injection (like an insulin shot). GCSF is given daily and Neulasta is given every 14 days instead of GCSF. Neulasta works like GCSF to help increase the white blood counts but lasts longer in your child's body.

This medicine will start if the ANC (absolute neutrophil count, a measure of the infection fighting cells) goes below 750 and will continue until it rises above 5000.

Expanded Access
Not Provided
Not Provided
  • Neuroblastoma
  • Metastatic Pheochromocytoma
  • Drug: 131 I-Metaiodobenzylguanidine (131 I-MIBG)
    131 I-MIBG 1-18mCi/kg given intravenously on day 1. Subjects may receive multiple courses every 4-8 weeks depending on the dose given.
    Other Names:
    • MIBG
    • 131 I-Metaiodobenzylguanidine
    • radioactive Iodine (131)
    • Metaiodobenzylguanidine
  • Drug: 131 I-MIBG
    131-I-MIBG will be infused intravenously over 60-90 minutes once per course. The dose will be determined by the treating physician.
    Other Names:
    • 131 I- Metaidobenzylguanidine
    • MIBG
    • Radioactive iodine
    • Metaiodobenzylguanidine therapy
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Available
Not Provided
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Refractory or relapsed neuroblastoma with original diagnosis based on tumor histopathology or elevated urine catecholamines with typical neuroblastoma cells in the bone marrow OR Metastatic Pheochromocytoma
  • Age greater than 1 year and able to cooperate with radiation safety restrictions during therapy period.
  • Performance Level: Patients must have a Karnofsky or Lansky performance status of equal to or greater than 50 percent
  • Disease status: Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any time (any new lesion or an increase in size of >25% of a pre-existing lesion).
  • Disease evaluable by MIBG scan must be present within 8 weeks of study entry and subsequent to any intervening therapy. The principal or co-investigator can waive the requirement for intervening therapy if in their judgment this would pose undue risk and would not affect ability to judge treatment effectiveness.
  • Stem cells: 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 1.0 x 106 CD34+ cells/kg
  • Prior Therapy: Patients may enter this study with or without re-induction therapy for recurrent tumor. Patients must have fully recovered from the toxic effects of any prior therapy. Subjects cannot be receiving chemotherapy, cytokine therapy or other investigational agents, and must have fully recovered from the toxic effects of any prior therapy.
  • Liver function: Bilirubin ≤2x upper limit of normal; AST/ALT ≤10x upper limit of normal
  • Kidney function: Creatinine ≤3x upper limit of normal
  • Signed informed consent: The patient and/or the patient's legally authorized guardian must provide written informed consent to participate in this expanded access protocol.

Exclusion criteria

  • Patients with disease of any major organ system that would compromise their ability to withstand therapy, as deemed by the principal investigator or treating sub-investigator.
  • Because of the teratogenic potential of the study medications, 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.
  • Patients who are on hemodialysis
  • Patients with uncontrolled infections
Both
1 Year and older
No
Contact: John Maris, MD maris@email.chop.edu
Contact: Yael Mosse, MD mosse@email.chop.edu
United States
 
NCT01163383
2005-02-4159
No
John Maris, Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
Not Provided
Principal Investigator: John M Maris, MD Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP