Clinical trial NCT00960739: Iodobenzylguanidine Meta-I131 and Topotecan in Young Patients With Refractory or Relapsed Metastatic Neuroblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: disseminated neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
stage 4S neuroblastoma
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
name: Novartis Pharmaceuticals
First posted: 2009-08-18
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate
timeFrame: Up to 12 months
Secondary outcomes:
measure: Toxicity
timeFrame: Up to 30 days after study treatment
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Toulouse
country: France
facility: Hôpital des Enfants
Study officials:
affiliation: Centre Oscar Lambret
name: Anne Sophie Defachelles, MD
role: PRINCIPAL_INVESTIGATOR
References: