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

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute, France
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT00960739
First received: August 16, 2009
Last updated: August 5, 2016
Last verified: August 2016
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Drug: Topotecan hydrochloride
Procedure: Autologous hematopoietic stem cell transplantation
Radiation: iobenguane I 131
Radiation: total-body irradiation
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • Response rate [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: Up to 30 days after study treatment ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: November 2008
Study Completion Date: July 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topotecan / 131-iodine MIBG association
  • 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). *
  • Iobenguane I 131: 444 MBq / kg of 131-iodine MIBG is administered on day 1 with activity up to 11,100 MBq per injection. *
  • A dosimetry is performed during hospitalization.
  • A second dose of 131-iodine MIBG (maximum 11 100 MBq) is administered to D21 so as to obtain a total body irradiation of 4 Gy. *
  • Autologous hematopoietic stem cell transplantation : Hematopoietic stem cells are reinjected 10 days after the second injection of 131-iodine MIBG.

    • If the dose of total-body irradiation of 4 Gy is reached during the first cycle, the second cycle is canceled.
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)
Other Name: Topotecan
Procedure: Autologous hematopoietic stem cell transplantation
Hematopoietic stem cells are reinjected 10 days after the second injection of 131-iodine MIBG
Other Name: hematopoietic stem cell transplantation
Radiation: iobenguane I 131
444 MBq / kg of 131-iodine MIBG is administered on day 1 with activity
Radiation: 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)

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

Ages Eligible for Study:   1 Year to 20 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00960739

Locations
France
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Hôpital des Enfants
Toulouse, France, 31059
Sponsors and Collaborators
Centre Oscar Lambret
National Cancer Institute, France
Novartis Pharmaceuticals
Investigators
Principal Investigator: Anne Sophie Defachelles, MD Centre Oscar Lambret
  More Information

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT00960739     History of Changes
Other Study ID Numbers: MIITOP-0607 
Study First Received: August 16, 2009
Last Updated: August 5, 2016
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Centre Oscar Lambret:
disseminated neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
stage 4S neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Iodine
Topotecan
3-Iodobenzylguanidine
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Radiopharmaceuticals

ClinicalTrials.gov processed this record on September 30, 2016