Clinical trial NCT00659984: N2007-01: Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma
Official title: A Phase 2a Study of Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
Lead sponsor: Molecular Insight Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-17
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Ultratrace™ Iobenguane I 131
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIBG), may carry radiation directly to tumor cells and not harm normal cells. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by I 131 MIBG.

PURPOSE: This phase II trial is studying the side effects and best dose of iodine I 131 MIBG followed by a stem cell transplant in treating young patients with relapsed or refractory high-risk neuroblastoma.

Detailed description: OBJECTIVES:

Primary

* To establish the maximum tolerated dose of iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) in patients with relapsed/refractory high-risk neuroblastoma.

Secondary

* To describe toxicity following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg \[3.7 MBq/kg\] (minimum dose of 1.0 mCi \[37 MBq\] but not to exceed 5.0 mCi \[185 MBq\]) intravenous administration of \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To describe, within the confines of a phase IIa trial, objective tumor response following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To explore dose-response following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To explore quality of life assessment following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.

OUTLINE:

* Dosimetry: Patients receive a dosimetric dose of iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) IV over 1-3 minutes. Patients then undergo 2 or 3 MIBG scans within 5 days of the dosimetry dose to assess biodistribution and tumor uptake. Patients with normal tumor uptake and biodistribution proceed to treatment.
* Treatment: Within 1-4 weeks of the dosimetric dose, patients with normal tumor uptake and biodistribution receive a therapeutic dose of \^131I-MIBG IV over 1 hour on day 0 and undergo MIBG scan on day 7. Patients then proceed to autologous stem cell infusion.
* Autologous stem cell infusion: Patients receive an infusion of autologous stem cells from peripheral blood or bone marrow on day 14. Patients with an ANC of \< 500/µl at any point after autologous stem cell infusion receive filgrastim (G-CSF) IV or subcutaneously once daily until ANC is \> 2,000/µl.

Patients complete a quality of life questionnaire at baseline and then at day 60.

After completion of study treatment, patients are followed at day 60 and periodically thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients must be at least one year and no more than 30 years of age when registered on this study.
* Patients must have high risk neuroblastoma and either have tumor left after treatment started at diagnosis or have had the tumor grow back (relapsed) after getting some treatment
* Patients must an MIBG scan done and it must be positive for neuroblastoma.
* Patients must have a PBSC or bone marrow stem cell product available that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell pheresis done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria.
* Patients must have adequate heart, lung, liver, kidney and bone marrow function.

Exclusion Criteria:

* They have had a stem cell transplant using another person as the stem cell donor. (You can still be in the study if a previous transplant used your own stem cells)
* They have other medical problems that could get much worse if they had this treatment.
* They are on dialysis for badly working kidneys or have other kidney problems.
* They are pregnant or breast feeding.
* They have tumor in the brain or spinal cord that is seen on a CT or MRI scan one month before starting treatment
* They had total body radiation or radiation to the entire belly.
* They have a known allergy to MIBG, iodine or SSKI.
* They can't cooperate with the special precautions that are needed during UltratraceTM MIBG treatment or with other safety monitoring requirements of the study..

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Day 60 +/-10 or Engraftment, whichever comes first
Secondary outcomes:
measure: Dose Limiting Toxicities
timeFrame: From the time of signed informed consent until Day 60 or until the end of therapy evaluation is completed (whichever comes first).
measure: Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions
timeFrame: Day 5 post Dosimetric Dose
measure: Overall Objective Tumor Response Post Therapeutic Treatment
timeFrame: Day 60 +/- 10 days post Therapeutic Dose
measure: Tumor Response in CT/MRI Lesions Post Therapeutic Treatment
timeFrame: Day 60 +/- 10 days post Therapeutic Dose
measure: Quality of Life
timeFrame: Day 60 +/- 10 days post Therapeutic Dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford University Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Comer Children's Hospital
state: Illinois
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: University of California, San Francisco
name: Katherine K. Matthay, MD
role: PRINCIPAL_INVESTIGATOR
References: