Clinical trial NCT03042429: Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients
Official title: Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neuroblastoma
Keywords: neuroblastoma
chemotherapy
autologous stem cell transplantation
radiotherapy
mIBG
tumor resection
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2017-02-03
Enrollment: 360
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, multi-center, non-blinded, prospective, controlled trial
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Event free survival
timeFrame: up to 9 years
Secondary outcomes:
measure: Overall survival
timeFrame: up to 9 years
measure: early response
timeFrame: up to 3 months
measure: late response
timeFrame: up to 9 months
Other outcomes:
Locations:
city: Koln
country: Germany
facility: University of Cologne
Study officials:
affiliation: University of Cologne
name: Frank Berthold, Prof.
role: STUDY_CHAIR
References:
citation: Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C. Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett. 2003 Jul 18;197(1-2):11-7. doi: 10.1016/s0304-3835(03)00076-4.
citation: Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, Klingebiel T, Kremens B, Schilling FH, Schrappe M, Simon T, Hero B. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005 Sep;6(9):649-58. doi: 10.1016/S1470-2045(05)70291-6.
citation: Langler A, Christaras A, Abshagen K, Krauth K, Hero B, Berthold F. Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood - a phase-II-study. Klin Padiatr. 2002 Jul-Aug;214(4):153-6. doi: 10.1055/s-2002-33175.
citation: Berthold F, Hero B. Neuroblastoma: current drug therapy recommendations as part of the total treatment approach. Drugs. 2000 Jun;59(6):1261-77. doi: 10.2165/00003495-200059060-00006.