Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients

Study Overview
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Brief Summary
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Improvement of event free survival of high-risk neuroblastoma patients by introduction of two additional topotecan containing chemotherapy cycles into the multimodal standard treatment (induction chemotherapy, myeloablative therapy, radiation, surgery as indicated, and consolidation therapy).

Detailed Description
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Experimental intervention (6 weeks + duration of the control intervention): 2 x N8 cycle (topotecan, cyclophosphamide, and etoposide) followed by standard arm treatment (i.e., control intervention) Control intervention (total duration 70-76 weeks): 3 x N5 cycle (cisplatin, etoposide, and vindesine) 3 x N6 cycle (vincristine, dacarbacine, ifosfamide, and doxorubicine), myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) 9 x retinoic acid cycles (6 months, 3 months break, 3 months) supportive care (PCP/fungal prophylaxis, transfusions, antibiotics, G-CSF)

Official Title
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Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-risk Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: Cycles N8, N5 and N6
* Drug: Cycles N5 and N6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: neuroblastoma stage 4 neuroblastoma and age ≥1 - 21 years or MYCN amplification and age ≥6 months - 21 years informed consent obtained Exclusion Criteria: Participation in other trials Pregnancy, lactation, or insufficient contraception for girls in childbearing age, Any concomitant non-protocol anticancer therapy, Incomplete initial staging.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Randomized, multi-center, non-blinded, prospective, controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental arm<br>Drug: Cycles N8, N5, and N6 Drug: topotecan, cyclophosphamide, and etoposide (N8 cycle) followed by Drug: cisplatin, etoposide, and vindesine (N5 cycle) and Drug: vincristine, dacarbacine, ifosfamide, and doxorubicine (N6 cycle) followed by myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) and by 9 x retinoic acid cycles (6 months, 3 months break, 3 months) | Drug: Cycles N8, N5 and N6<br>* two chemotherapy cycles N8 followed by standard arm therapy<br>* Other names: topotecan, cyclophosphamide, etoposide;|
| Active Comparator: standard arm<br>Drug: Cycles N5 and N6 Drug: cisplatin, etoposide, and vindesine (N5 cycle) and Drug: vincristine, dacarbacine, ifosfamide, and doxorubicine (N6 cycle) followed by myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) and by 9 x retinoic acid cycles (6 months, 3 months break, 3 months) | Drug: Cycles N5 and N6<br>* Standard arm six chemotherapy cycles (3xN5 and 3x N6) followed by myeloablative therapy with stem cell support and isotretinoin<br>* Other names: cisplatin, vindesine, ifosfamide, dacarbacine, doxorubicine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | days from diagnosis to Event or last follow-up | up to 9 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | days from diagnosis to death or last follow-up | up to 9 years | 
| early response | remission status (INRG) measured after 2 chemotherapy cycles | up to 3 months | 
| late response | remission status (INRG) measured before stem cell transplant | up to 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, mIBG, tumor resection, neuroblastoma, chemotherapy, autologous stem cell transplantation