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

NCT03042429 | Completed Phase 3 DMC

• 1 other identifier: UCologne
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

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).

Conditions

Neuroblastoma

Keywords

neuroblastoma; chemotherapy; autologous stem cell transplantation; radiotherapy; mIBG; tumor resection

Outcome Measures

Primary Outcomes (1)

• Event free survival

  days from diagnosis to Event or last follow-up

  up to 9 years

Secondary Outcomes (3)

• Overall survival

  up to 9 years

• early response

  up to 3 months

• late response

  up to 9 months

Study Arms (2)

experimental arm

EXPERIMENTAL

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

standard arm

ACTIVE COMPARATOR

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

Interventions

Cycles N8, N5 and N6 DRUG

two chemotherapy cycles N8 followed by standard arm therapy

Also known as: topotecan, cyclophosphamide, etoposide

experimental arm

Cycles N5 and N6 DRUG

Standard arm six chemotherapy cycles (3xN5 and 3x N6) followed by myeloablative therapy with stem cell support and isotretinoin

Also known as: cisplatin, vindesine, ifosfamide, dacarbacine, doxorubicine

standard arm

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• neuroblastoma
• stage 4 neuroblastoma and age ≥1 - 21 years or MYCN amplification and age ≥6 months - 21 years
• informed consent obtained

You may not qualify if:

• Participation in other trials
• Pregnancy, lactation, or insufficient contraception for girls in childbearing age,
• Any concomitant non-protocol anticancer therapy,
• Incomplete initial staging.

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (1)

University of Cologne

Cologne, 50924, Germany

Location

Related Publications (4)

• 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.

  PMID: 12880954 RESULT

• 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.

  PMID: 16129365 RESULT

• 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.

  PMID: 12165894 RESULT

• 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.

  PMID: 10882162 RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

Topotecan; Cyclophosphamide; Etoposide; Cisplatin; Vindesine; Ifosfamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Oxazines; Heterocyclic Compounds, 1-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Study Officials

• Frank Berthold, Prof.

  University of Cologne

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: no masking
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: Randomized, multi-center, non-blinded, prospective, controlled trial

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 3, 2017
• Study Start: January 1, 2007
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: February 6, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)