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

Centre Oscar Lambret

Status and phase: Completed; Phase 2

Conditions: Neuroblastoma

Treatments: Radiation: total-body irradiation; Radiation: iobenguane I 131; Procedure: Autologous hematopoietic stem cell transplantation; Drug: Topotecan hydrochloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00960739

MIITOP-0607

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 1 to 20 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Topotecan / 131-iodine MIBG association

Experimental group

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.

Treatment:

Radiation: iobenguane I 131

Drug: Topotecan hydrochloride

Procedure: Autologous hematopoietic stem cell transplantation

Radiation: total-body irradiation