NeuroblastomaPhase 3NB2004-HRNCT03042429
Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients
A Phase 3 study testing Cycles N8, N5 and N6 and Cycles N5 and N6 in people with Neuroblastoma, run by University of Cologne at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Cycles N8, N5 and N6 and Cycles N5 and N6
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2007to 31 Dec 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- neuroblastoma
- stage 4 neuroblastoma and age ≥1 - 21 years or MYCN amplification and age ≥6 months - 21 years
- informed consent obtained
Who cannot join
- Participation in other trials
- Pregnancy, lactation, or insufficient contraception for girls in childbearing age,
- Any concomitant non-protocol anticancer therapy,
- Incomplete initial staging.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-risk Neuroblastoma
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).
Read the 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)
- Conditions
- Neuroblastoma
- Being tested
- Cycles N8, N5 and N6, Cycles N5 and N6
- Keywords
- neuroblastoma, chemotherapy, autologous stem cell transplantation, radiotherapy, mIBG, tumor resection
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cycles N8, N5 and N6Drug
Also called topotecan, cyclophosphamide, etoposide
two chemotherapy cycles N8 followed by standard arm therapy
Cycles N5 and N6Drug
Also called cisplatin, vindesine, ifosfamide, dacarbacine, doxorubicine
Standard arm six chemotherapy cycles (3xN5 and 3x N6) followed by myeloablative therapy with stem cell support and isotretinoin
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Cycles N5 and N6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival
days from diagnosis to Event or last follow-up
Measured: up to 9 years
Secondary outcomes (3)
Overall survival
days from diagnosis to death or last follow-up
Measured: up to 9 years
early response
remission status (INRG) measured after 2 chemotherapy cycles
Measured: up to 3 months
late response
remission status (INRG) measured before stem cell transplant
Measured: up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2017 (estimated)
- Study start1 Jan 2007
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Randomized, multi-center, non-blinded, prospective, controlled trial
- Masking
- None (open label)
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frank Berthold, University of Cologne
- Investigators
- Frank Berthold, Prof., Study chair, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03042429
- Sponsor's protocol ID
- UCologne
- Acronym
- NB2004-HR
- Status last verified
- Feb 2017
- First submitted
- 1 Feb 2017
- Last updated
- 6 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 12880954Berthold 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.
PubMed 16129365Langler 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.
PubMed 12165894Berthold 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.
PubMed 10882162
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT03042429
- Acronym / sponsor ID
- NB2004-HR / UCologne
- Conditions
- Neuroblastoma
- Keywords
- neuroblastoma, chemotherapy, autologous stem cell transplantation, radiotherapy, mIBG, tumor resection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- 1 Jan 2007 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 3 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, multi-center, non-blinded, prospective, controlled trial
| Arm | Type | Receives |
|---|---|---|
| experimental arm | Experimental | Drug: Cycles N8, N5 and N6Drug: 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) |
| standard arm | Active comparator | Drug: Cycles N5 and N6Drug: 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) |
Who may qualify
- Ages
- 6 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- neuroblastoma
- stage 4 neuroblastoma and age ≥1 - 21 years or MYCN amplification and age ≥6 months - 21 years
- informed consent obtained
Key exclusion criteria (4 listed)
- Participation in other trials
- Pregnancy, lactation, or insufficient contraception for girls in childbearing age,
- Any concomitant non-protocol anticancer therapy,
- Incomplete initial staging.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cycles N8, N5 and N6Also: topotecan, cyclophosphamide, etoposidetwo chemotherapy cycles N8 followed by standard arm therapy | Drug | experimental arm |
| Cycles N5 and N6Also: cisplatin, vindesine, ifosfamide, dacarbacine, doxorubicineStandard arm six chemotherapy cycles (3xN5 and 3x N6) followed by myeloablative therapy with stem cell support and isotretinoin | Drug | standard arm |
Primary outcome
Event free survival
Time frame: up to 9 years
days from diagnosis to Event or last follow-up
3 secondary outcomes
Overall survival
Time frame: up to 9 years
early response
Time frame: up to 3 months
late response
Time frame: up to 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2017.
- Results publication: PubMed 12880954Berthold 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.
- Results publication: PubMed 16129365Berthold 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.
- Results publication: PubMed 12165894Langler 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.
- Results publication: PubMed 10882162Berthold 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Berthold, Prof. study chair
University of Cologne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cycles N8, N5 and N6 and Cycles N5 and N6 in people with Neuroblastoma, run by University of Cologne at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (time frame: up to 9 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03042429, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2017.