NCT01019850

N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma

Vorinostat With 131-I MIBG Therapy for Resistant/Relapsed Neuroblastoma: A Phase I Study IND# 105,744

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: New Approaches to Neuroblastoma Therapy Consortium · Academic / Other
• Sex: All
• Age: 2 Years – 30 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as iobenguane I 131, may carry radiation directly to tumor cells and not harm normal cells. Giving vorinostat together with iobenguane I 131 may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving vorinostat together with iobenguane I 131 in treating patients with resistant or relapsed neuroblastoma.

Detailed description

OBJECTIVES: Primary * To determine the maximum tolerated dose of vorinostat in combination with iobenguane I 131 in patients with resistant or relapsed neuroblastoma. * To define the toxicities of vorinostat in combination with therapeutic doses of iobenguane I 131 in these patients. Secondary * To describe, within the context of a phase I study, the response rate in patients treated with vorinostat and iobenguane I 131. * To describe histone acetylation levels and norepinephrine transporter mRNA levels in peripheral blood mononuclear cells after treatment with different doses of vorinostat. OUTLINE: This is a multicenter study. Patients receive oral vorinostat once daily on days 1-14 and iobenguane I 131 IV over 1½-2 hours on day 3. Patients undergo autologous peripheral blood stem cell transplantation on day 17. Blood samples may be collected periodically for correlative biological studies. After completion of study treatment, patients are followed up periodically.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	Vorinostat	Patients on study will receive vorinostat orally once daily on days 1 to 14 of treatment.This is a single course treatment. The study has a planned dose escalation schedule, the starting dose level is 180 mg/M2.The maximum absolute dose of vorinostat is 400 mg.
RADIATION	131- I Metaiodobenzylguanidine	Patients will receive 131-I MIBG on day 3 , one hour after vorinostat dosing.Patients will initially receive 8 mCi/kg 131-I MIBG with 180 mg/m2/dose vorinostat. The dose of 131-I MIBG will be escalated in subsequent cohorts to 15 mCi/kg and then to 18 mCi/kg.If the starting dose exceeds the maximum tolerated dose, patients will be treated with a lowering of vorinostat dose initially (150 mg/m2/day . Dose level -1). If this combination still exceeds the maximum tolerated dose, then a dose level using reduced dose 131-I MIBG will be studied (6 mCi/kg. Dose level -2).
PROCEDURE	Peripheral Blood Stem Cell Infusion	Stem cell infusion is planned for 2 weeks after MIBG infusion (day 17). However, stem cells may be infused on day 18 or day 19 to avoid weekend or holiday stem cell infusions.The dose for Purged PBSC is a minimum of 2 x 106 viable CD34+ cells/kg and for Unpurged PBSC: a minimum of 2 x 106 viable CD34+ cells/kg must be available. Stem cells must be infused over 15-30 minutes and within 1.5 hours of thawing.Stem cells will be infused following institutional guidelines for prophylaxis of hypersensitivity reactions and monitoring.
DRUG	Filgrastim	All patients will receive filgrastim following hematopoietic stem cell infusion according to institutional guidelines (section 4.2.3 of protocol).

Timeline

• Start date: 2010-03-01
• Primary completion: 2014-12-01
• Completion: 2015-02-01
• First posted: 2009-11-25
• Last updated: 2023-04-10

Locations

12 sites across 1 country: United States