NCT01313936

High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma

Pilot Study of High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed High-Risk Neuroblastoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	Metaiodobenzylguanidine (MIBG)	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.

Timeline

• Start date: 2011-03-01
• Primary completion: 2014-05-01
• Completion: 2014-05-01
• First posted: 2011-03-14
• Last updated: 2019-04-29
• Results posted: 2015-08-07

Locations

1 site across 1 country: United States