Iodobenzylguanidine Meta-I131 and Topotecan in Young Patients With Refractory or Relapsed Metastatic Neuroblastoma

Neuroblastoma Clinical Trial

— MIITOP  

Official title:

Phase II Study of the Association of Iodobenzylguanidine Meta-I131 (I131 MIBG) and Topotecan in the Treatment of Refractory or Relapsed Metastatic Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00960739
• Other study ID #: MIITOP-0607
• Status: Completed
• Phase: Phase 2
• First received: August 16, 2009
• Last updated: August 5, 2016
• Start date: November 2008
• Est. completion date: July 2016

Study information

• Verified date: August 2016
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radioactive drugs, such as iodobenzylguanidine meta-I131, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A stem cell transplant may be able to replace the cells that were destroyed by iodobenzylguanidine meta-i131 and topotecan hydrochloride.

PURPOSE: This phase II trial is studying the side effects of iodobenzylguanidine meta-I131 given together with topotecan hydrochloride and to see how well it works in treating young patients with refractory or relapsed metastatic neuroblastoma.

Description:

OBJECTIVES:

Primary

• Determine the antitumor activity of iodobenzylguanidine meta-I131 (^131I-MIBG) and topotecan in young patients with refractory or relapsed metastatic neuroblastoma.

Secondary

• Determine the hematological and extra-hematological toxicities of this regimen.

OUTLINE: This is a multicenter study.

During the 21 days before treatment begins, autologous peripheral blood stem cells (PBSC) are collected.

Patients receive topotecan hydrochloride IV over 30 minutes daily on days 1-5 and iodobenzylguanidine meta-^131I IV over 2 hours on day 1. Treatment repeats every 21 days for 2 courses. Patients also undergo total-body irradiation.

On day 10 of the second course, autologous PBSC are reinfused.

After completion of study therapy, patients are followed at 6 and 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 20 Years

Eligibility

Inclusion criteria:

• Histologically confirmed neuroblastoma

• Metastatic disease that is recurrent or refractory to induction therapy

• Primary or metastatic tumor target with MIBG fixation (tumor/soft tissue) > 2

• Autologous bone marrow or peripheral blood stem cells must be available

• WHO performance status (PS) 0-1 OR Lansky PS 70-100%

• Life expectancy > 2 months

• ANC = 1,000/mm³

• Platelet count = 100,000/mm³

• Creatinine clearance normal for age

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No prior hypersensitivity to topotecan or its excipients

• No toxicity to other organs = NCI-CTCAE v3.0 grade 2

• No other debilitating disease

• No HIV positivity

• More than 30 days since prior external-beam radiation (6 weeks if cranio-spinal, abdominal, or pulmonary)

• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)

• No other contraindicated biologic therapy that cannot be discontinued for = 4 courses during MIBG therapy

Exclusion criteria:

• Pregnancy or breastfeeding women

• HIV positive

• Participation to another phase I,II or III clinical trial

• Other invalidating pathology

• Concomitant treatment interfering with MIBG

• Hypersensibility to Topotecan

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• Topotecan hydrochloride
The topotecan hydrochloride is administered intravenously over five days to dose of 0.7 mg/ m²/day from day 1 to day 5 (first cycle), then from day 21 to day 25 (second cycle)

Procedure:
• Autologous hematopoietic stem cell transplantation
Hematopoietic stem cells are reinjected 10 days after the second injection of 131-iodine MIBG

Radiation:
• iobenguane I 131
444 MBq / kg of 131-iodine MIBG is administered on day 1 with activity
• total-body irradiation
the dose of total-body irradiation of 4 Gy is reached during the first cycle, the second cycle is canceled (131-iodine MIBG and Topotecan)

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	Hôpital des Enfants	Toulouse

Sponsors (3)

Lead Sponsor	Collaborator
Centre Oscar Lambret	National Cancer Institute, France, Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate		Up to 12 months	No
Secondary	Toxicity		Up to 30 days after study treatment	Yes