Informations générales (source: ClinicalTrials.gov)
Randomized Open-label Non-inferiority Phase 3 Clinical Trial for Patients With a Stage IV Childhood Renal Tumor, Comparing Upfront Vincristine, Actinomycin-D and Doxorubicin (Standard Arm) With Upfront Vincristine, Carboplatin and Etoposide (Experimental Arm)
Interventional
Phase 3
Assistance Publique Hopitaux De Marseille (Voir sur ClinicalTrials)
février 2023
octobre 2033
29 août 2025
Nephroblastoma (Wilms tumor, WT) is the most common renal tumor of childhood representing
± 6% of all childhood malignancies. The diagnosis is established on clinical and
radiological grounds. Metastases are visible on conventional imaging in at least 12% of
nephroblastoma patients; however, an additional ~15% of patients have nodules on CT-scan
only. The treatment consists of neoadjuvant (preoperative) chemotherapy, nephrectomy and
risk-based adjuvant chemotherapy ± radiation therapy (RT) to the flank and/or metastases.
For truly localized tumors, overall survival is > 85% (high risk histology excluded).
Several high risk biological characteristics have been identified: diffuse anaplasia,
gain of 1q chromosome, loss of heterozygosity 1p + 16q, blastemal residual volume.
For metastatic nephroblastoma, the standard neo-adjuvant chemotherapy includes 3 drugs:
vincristine, actinomycin-D and doxorubicin (VAD). Long-term survival is 82% (1). However,
two issues arise. First, the use of doxorubicin ± concomitant RT might be associated with
cardiac and pulmonary sequelae (4-17% of congestive heart failure) (2), and actinomycin-D
is associated with hepatic toxicity (3). Second, patients with "CT-only" nodules are
treated according to "localized disease". However, their outcome is poorer than that of
truly "localized disease" (4-6).
The efficacy of carboplatin and etoposide is known for a long time; these drugs are used
as second line treatment or for high-risk histology nephroblastoma. Therefore, an
alternate chemotherapy has been designed that combines drugs shown as highly efficacious
in nephroblastoma, i.e., Vincristine, Carboplatin and Etoposide (VCE). VCE has been used
for the treatment of other pediatric malignancies. For metastatic nephroblastoma, the
switch from VAD to VCE and the associated reduction of actinomycin-D and doxorubicin is
expected to reduce the chemotherapy-related long-term toxicity. In addition, VCE could
potentially decrease the rate of patients requiring pulmonary RT. Finally VCE may have a
beneficial effect on tumor high risk biological characteristics.
French patients with nephroblastoma have been treated for > 40 years according to SIOP
protocols collaborating in the SIOP Renal Tumour Study Group (SIOP-RTSG). This group has
designed an international randomized phase III clinical trial for the evaluation of VCE
versus VAD in patients with metastatic renal tumors (>>90% having nephroblastoma), in
order to decrease the long-term toxicity while at least preserving, if not improving, the
treatment efficacy. In addition, the issue of "CT-only" nodules and their adequate
treatment needs to be solved. In previous protocols, the treatment strategy was based on
the diagnosis of pulmonary metastases (~90% of all metastases) by conventional pulmonary
X-ray. Central Radiological Review (CRR) is planned for the initial staging using CT ±
MRI, as it is expected to more accurately detect patients with metastatic disease,
including patients with "CT-only" nodules. In addition, CRR will be set up for real-time
response assessment during treatment, in order to reliably determine who require
pulmonary RT and which postoperative chemotherapy.
Therefore, the main trial objectives are:
- Explore the non-inferiority (efficacy) of neoadjuvant VCE chemotherapy (experimental
arm) as compared to the standard arm with VAD.
- Provide central radiological review (CRR) at diagnosis and after neoadjuvant
chemotherapy in order to determine more precisely the appropriate treatment for each
patient.
The primary objective of the RCT is to investigate the metastatic complete response rate
(MetCR, including very good partial response (VGPR)) of neoadjuvant 6 weeks of VAD as
compared to neoadjuvant VCE in stage IV renal tumours using CRR. Several international
studies have shown that MetCR is a good surrogate endpoint for survival.
The postoperative treatment, secondary objectives as well as the intended methodology are
detailed in the research project.
The total number of patients is 406 patients for the entire phase III trial running in
the 12 major SIOP countries (max 110 patients in France).
The expected trial duration is 5 years for accrual + 2 years follow-up (the overall
10-year follow-up for long-term toxicity will be an independently funded ancillary study.
This duration is required for a reliable evaluation of the cardiac toxicity).
The results of the current trial should be useful for the future protocols for the
treatment of all patients with nephroblastoma (metastatic but also localized and
bilateral).
The results of this RCT will be worthy for the entire international pediatric oncology
community and future patients throughout the world and will be communicated in scientific
congresses and high-level peer-reviewed journals.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Claudia PASQUALINI | 10/06/2026 06:40:05 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Assistance Publique Hopitaux de Marseille - Marseille - France | ARNAULD VERSCHUUR | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- suffering from metastatic renal tumour at initial diagnosis
- having at least one circumscript, non-calcified (pulmonary) nodule (or other lesion
highly suspicious of metastasis according to criteria for metastatic disease) ≥ 3 mm
as determined by chest CT-scan and abdominal CT-scan/MRI.
- Metastatic disease must be confirmed by central review.
- suffering from metastatic renal tumour at initial diagnosis
- having at least one circumscript, non-calcified (pulmonary) nodule (or other lesion
highly suspicious of metastasis according to criteria for metastatic disease) ≥ 3 mm
as determined by chest CT-scan and abdominal CT-scan/MRI.
- Metastatic disease must be confirmed by central review.
-