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

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Topotecan hydrochloride
Autologous hematopoietic stem cell transplantation
iobenguane I 131
total-body irradiation
Sponsored by
Centre Oscar Lambret
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, stage 4S neuroblastoma

Eligibility Criteria

1 Year - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre Oscar Lambret
  • Centre Léon Bérard
  • Hôpital des Enfants

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Topotecan / 131-iodine MIBG association

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate

Secondary Outcome Measures

Toxicity

Full Information

First Posted
August 16, 2009
Last Updated
August 5, 2016
Sponsor
Centre Oscar Lambret
Collaborators
National Cancer Institute, France, Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00960739
Brief Title
Iodobenzylguanidine Meta-I131 and Topotecan in Young Patients With Refractory or Relapsed Metastatic Neuroblastoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Oscar Lambret
Collaborators
National Cancer Institute, France, Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, stage 4S neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topotecan / 131-iodine MIBG association
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Topotecan hydrochloride
Other Intervention Name(s)
Topotecan
Intervention Description
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)
Intervention Type
Procedure
Intervention Name(s)
Autologous hematopoietic stem cell transplantation
Other Intervention Name(s)
hematopoietic stem cell transplantation
Intervention Description
Hematopoietic stem cells are reinjected 10 days after the second injection of 131-iodine MIBG
Intervention Type
Radiation
Intervention Name(s)
iobenguane I 131
Intervention Description
444 MBq / kg of 131-iodine MIBG is administered on day 1 with activity
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Intervention Description
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)
Primary Outcome Measure Information:
Title
Response rate
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Toxicity
Time Frame
Up to 30 days after study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Sophie Defachelles, MD
Organizational Affiliation
Centre Oscar Lambret
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Hôpital des Enfants
City
Toulouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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