High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a pilot study to determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are
      tolerable when given with irinotecan/vincristine on a one week schedule to children and young
      adults with high-risk refractory/relapsed neuroblastoma.
    

Detailed description: 
      131I-metaiodobenzylguanidine (131I-MIBG) is an active therapy in patients with widely
      metastatic, treatment-resistant neuroblastoma, where response rates are 20-40% at doses (>
      15mCi/kg) requiring stem cell rescue. Irinotecan is a topoisomerase I inhibitor with
      single-agent chemotherapeutic activity against neuroblastoma and other pediatric solid tumors
      in phase I and II clinical trials. With more protracted schedules (e.g. daily for 5 days/week
      x 2 weeks), the major dose-limiting toxicity is diarrhea. With shorter schedules,
      myelosuppression becomes dose-limiting. In adult solid tumors, irinotecan has been an
      effective radiosensitizer and is currently being evaluated by the Children's Oncology Group
      for this purpose in rhabdomyosarcoma protocols incorporating external beam radiotherapy.

      Compared to single-agent 131I-MIBG, the combination of topotecan (a related camptothecin) and
      131I-MIBG demonstrated superior pre-clinical activity in mouse xenograft models of
      neuroblastoma. This combination had no unexpected toxicities in a pilot clinical study. We
      have completed a clinical trial of vincristine, irinotecan, 131I-MIBG that utilized
      irinotecan on a protracted schedule (5 days per week x 2 weeks). The rationale for this
      schedule was to provide a greater degree of overlap between the radiation sensitizer
      (irinotecan) and the radiation exposure provided following 131I-MIBG infusion. This
      combination was shown to be tolerable at doses up to 18 mCi/kg 131I-MIBG. However, more
      patients experienced grade 2 and 3 diarrhea than would be customary with the dose and
      schedule of irinotecan used in that trial. It is therefore of interest to determine whether
      this combination of irinotecan, vincristine, and 131I-MIBG will be better tolerated using
      irinotecan at higher doses in a shorter schedule. The current standard schedule in Children's
      Oncology Group protocols for the combination of vincristine, irinotecan is now a higher dose
      in five, rather than 10 days. In the current pilot study, we will evaluate the tolerability
      and anti-tumor activity of this combination using irinotecan given once daily for 5 days
      only. Two 131I-MIBG dose levels will be evaluated. This study will provide the basis for a
      future randomized trial.
    

Intervention name(s): Metaiodobenzylguanidine (MIBG)
Intervention type(s): Drug
Intervention description(s): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.
Other intervention name(s): 131I-MIBG
Intervention MeSH terms: 3-Iodobenzylguanidine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neuroblastoma; MIBG; 131I-MIBG; Irinotecan; Vincristine; Resistant; Relapsed; Treatment; UCSF; Pediatric; Oncology