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

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

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.

Study Overview

• Status: Completed
• Conditions: Neuroblastoma
• Intervention / Treatment: Drug: Topotecan hydrochloride; Procedure: Autologous hematopoietic stem cell transplantation; Radiation: iobenguane I 131; Radiation: total-body irradiation

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Toulouse, France, 31059
    • Hôpital Des Enfants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Topotecan; Procedure: Autologous hematopoietic stem cell transplantation; Hematopoietic stem cells are reinjected 10 days after the second injection of 131-iodine MIBG; Other Names: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity	Up to 30 days after study treatment

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: Novartis Pharmaceuticals; National Cancer Institute, France
• Investigators: Principal Investigator: Anne Sophie Defachelles, MD, Centre Oscar Lambret

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 16, 2009
• First Submitted That Met QC Criteria: August 16, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Estimate): August 8, 2016
• Last Update Submitted That Met QC Criteria: August 5, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: disseminated neuroblastoma; localized unresectable neuroblastoma; recurrent neuroblastoma; stage 4S neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Radiopharmaceuticals; Topoisomerase I Inhibitors; Topotecan; 3-Iodobenzylguanidine
• Other Study ID Numbers: MIITOP-0607

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No