B2004 Trial Protocol for Risk Adapted Treatment of Children with Neuroblastoma
- Conditions
- C74.9Adrenal gland, unspecified
- Registration Number
- DRKS00001038
- Lead Sponsor
- niversitätsklinik KölnPädiatrische Onkologie und Hämatologie
- Brief Summary
Background: Long-term survival of high-risk neuroblastoma patients is still below 50% despite intensive multimodal treatment. This trial aimed to address whether the addition of two topotecan-containing chemotherapy courses compared to standard induction therapy improves event-free survival (EFS) of these patients. Patients and methods: An open-label, multicenter, prospective randomized controlled trial was carried out at 58 hospitals in Germany and Switzerland. Patients aged 1-21 years with stage 4 neuroblastoma and patients aged 6 months to 21 years with MYCN-amplified tumors were eligible. The primary endpoint was EFS. Patients were randomly assigned to standard induction therapy with six chemotherapy courses or to experimental induction chemotherapy starting with two additional courses of topotecan, cyclophosphamide, and etoposide followed by standard induction chemotherapy (eight courses in total). After induction chemotherapy, all patients received high-dose chemotherapy with autologous hematopoietic stem cell rescue and isotretinoin for consolidation. Radiotherapy was applied to patients with active tumors at the end of induction chemotherapy. Results: Of 536 patients enrolled in the trial, 422 were randomly assigned to the control arm (n = 211) and the experimental arm (n = 211); the median follow-up time was 3.32 years (interquartile range 1.65-5.92). At data lock, the 3-year EFS of experimental and control patients was 34% and 32% [95% confidence Interval (CI) 28% to 40% and 26% to 38%; P = 0.258], respectively. Similarly, the 3-year overall survival of the patients did not differ [54% and 48% (95% CI 46% to 62% and 40% to 56%), respectively; P = 0.558]. The response to induction chemotherapy was not different between the arms. The median number of non-fatal toxicities per patient was higher in the experimental group while the median number of toxicities per chemotherapy course was not different. Conclusion: While the burden for the patients was increased by prolonging the induction chemotherapy and the toxicity, the addition of two topotecan-containing chemotherapy courses did not improve the EFS of high-risk neuroblastoma patients and thus cannot be recommended.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 1629
Diagnosis of neuroblastoma by histology using tumor tissue or as evidenced by the
presence of distinct neuroblastoma cells in the bone marrow AND elevated
catecholamine metabolites (i.e., homovanillic acid [HVA] and vanillylmandelic acid
[VMA]) in blood or urine
- Newly diagnosed disease (for patients in the low-risk group)
- Diagnosis from tumor tissue (for patients in the medium-risk group)
- Meets criteria for 1 of the following risk groups:
Low-risk group:
- No MYCN amplification AND meets 1 of the following criteria:
- Stage 1 disease
- Stage 2 disease with no chromosome 1p deletion or imbalance
- Stage 3 disease with no chromosome 1p deletion or imbalance (for
patients < 2 years of age)
- Stage 4S disease (for patients < 1 year of age)
Medium-risk group:
- No MYCN amplification AND meets 1 of the following criteria:
- Stage 2 disease with chromosome 1p deletion or imbalance
- Stage 3 disease with chromosome 1p deletion or imbalance
- Any chromosome 1p status (for patients = 2 years of age)
- Stage 4 disease (for patients < 1 year of age)
High-risk group, meeting 1 of the following criteria:
- Any stage disease with MYCN amplification
- Any MYCN status (for patients = 1 year of age)
PATIENT CHARACTERISTICS:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Prior nephrectomy or other mutilating surgery as initial surgery (for patients in
the low-risk group)
- Other concurrent anticancer therapy
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Event-free survival (EFS) [Time Frame: No]<br>Locoregional EFS [Time Frame: No]
- Secondary Outcome Measures
Name Time Method