Randomized phase 3 clinical trial for patients with metastasized childhood renal tumour

Randomized multi-centre open-label non-inferiority phase 3 clinical trial for patients with a stage IV childhood renal tumour comparing upfront Vincristine, Actinomycin-D and Doxorubicin (VAD, standard arm) with upfront Vincristine, Carboplatin and Etoposide (VCE, experimental arm)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-000533-13-AT

Enrollment

406

Registered

2021-01-18

Start date

2021-02-25

Completion date

Unknown

Last updated

2024-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stage IV childhood renal tumours

Interventions

Trade Name: LYOVAC-COSMEGEN Product Name: D-Actinomycin Pharmaceutical Form: Solution for infusion INN or Proposed INN: dactinomycin CAS Number: 50-76-0 Other descriptive name: DACTINOMYCIN Concentrat

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Children 3months - Patients 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 (for radiological details please refer to section 12.8). - Metastatic childhood renal tumour must be confirmed by central review. - Signed informed consent form(s) prior to study entry according to national guidelines and GCP guidelines - Understand and voluntarily provide permission (subjects and when applicable, parental/legal representative(s)) to the ICF prior to conducting any study related assessments/procedures - Able to adhere to the study visit schedule and other protocol requirements - No pre-existing and ongoing cardiac malfunction disease (insufficiency, malign arrhythmias) - No pre-existing and ongoing liver function deficiency that is not controllable by substitution Are the trial subjects under 18? yes Number of subjects for this age range: 406 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - inability to be followed until two years after treatment - other chemotherapy prior to enrolment - Patient and/or parental/legal representative(s) denied randomization - primary nephrectomy - histology other than nephroblastoma if confirmed by upfront tumour biopsy/cutting needle biopsy - pregnancy or lactation - Fertile female with child bearing potential and fertile male subjects who refuse using highly effective contraceptive measures - Treated by any investigational agent in a clinical study within previous 4 weeks - hypersensitivity to the active substances or other excipients contained in the investigational medical products listed in the summary of product characteristics (SmPC) or Investigators Brochure (IB). - unwillingness to follow adequate supportive measures including transfusion of blood products if medically needed - inability to receive chemotherapy according to the protocol, this is particulary true for: a. acute kidney failure needing dialysis treatment b. pre-existing peripheral neuropathy - Active, uncontrolled life threatening Infection (e.g. Acute Hepatitis, Pneumonia, AIDS, Varizella) - known chromosomal instability/susceptibility (e.g. Fanconi Anemia, Nejjmegen Breakage Syndrome) - participation in other interventional trials (registration in observational non-interventional studies is acceptable) - age at start of treatment 18 years - any other medical condition incompatible with the protocol treatment

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine non-inferiority of upfront 6 weeks of VCE to VAD in the overall metastatic response rate (MetRR) in newly diagnosed stage 4 WT. The MetRR will include the pulmonary response rate (PRR) and the response rate on non-pulmonary metastasis (NPRR).;Secondary Objective: - acute toxicitiy of preoperative chemotherapy - histological composition and local stage distribution of the primary tumour - tumour volume reduction - EFS and OS after 2 and 5 years - short term and long term effects - role of molecular markers - assess and review the standard imaging criteria in use of pulmonary matastases - investigating the imaging characteristics of lung metastasis in routine chest imaging in correlation with outcome;Primary end point(s): Percentage of patients with radiologic complete response (CR) of any metastasis and/or Very Good Partial Response (VGPR) of lung metastasis of childhood renal tumours after 6 weeks of preoperative chemotherapy (Section 12.5 for definitions of metastatic response);Timepoint(s) of evaluation of this end point: 6 weeks after start of preoperative chemotherapy of the last patient	—

Measure

Time frame

Main Objective: To determine non-inferiority of upfront 6 weeks of VCE to VAD in the overall metastatic response rate (MetRR) in newly diagnosed stage 4 WT. The MetRR will include the pulmonary response rate (PRR) and the response rate on non-pulmonary metastasis (NPRR).;Secondary Objective: - acute toxicitiy of preoperative chemotherapy - histological composition and local stage distribution of the primary tumour - tumour volume reduction - EFS and OS after 2 and 5 years - short term and long term effects - role of molecular markers - assess and review the standard imaging criteria in use of pulmonary matastases - investigating the imaging characteristics of lung metastasis in routine chest imaging in correlation with outcome;Primary end point(s): Percentage of patients with radiologic complete response (CR) of any metastasis and/or Very Good Partial Response (VGPR) of lung metastasis of childhood renal tumours after 6 weeks of preoperative chemotherapy (Section 12.5 for definitions of metastatic response);Timepoint(s) of evaluation of this end point: 6 weeks after start of preoperative chemotherapy of the last patient

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Secondary

Measure	Time frame
Secondary end point(s): - Radiologic response to preoperative treatment: Metastatic response assessment: - Percentage of patients after 6 weeks of preoperative chemotherapy achieving a CR after surgery of metastasis at time of nephrectomy - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after 6 weeks of preoperative chemotherapy + 9 weeks adjuvant chemotherapy. - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after preoperative chemotherapy + 9 weeks adjuvant chemotherapy + metastasectomy - Percentage of patients with remaining metastatic disease after surgery that achieve a CR at week 9 of adjuvant chemotherapy - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma at the end of adjuvant chemotherapy ± metastasectomy ± RT - Percentage of patients with radiologic complete response (CR) of any metastasis or Very Good Partial Response (VGPR) of lung metastasis of nephroblastoma after 6 weeks of preoperative chemotherapy of patients with remaining metastatic disease after surgery that achieve a CR at week 9 of adjuvant chemotherapy - Primary tumour volume shrinkage after 6 weeks of preoperative chemotherapy - Primary tumour volume after 6 weeks of preoperative chemotherapy - Number of metastases at diagnosis and after preoperative treatment - Maximum diameters of the largest metastases at diagnosis and after preoperative treatment - Histologic & molecular response to preoperative treatment: - Stage distribution of local tumour - Histologic subtype distribution of local tumour (LR, IR, HR) - Histologic subtype distribution of resected nodules/metastsis (LR, IR, HR) - Percentage of blastema and blastemal residual volume in local tumour - Percentage of patients with <10 ml of blastemal residual volume in resected nephroblastoma after 6 weeks of preoperative ch	—

Measure

Time frame

Secondary end point(s): - Radiologic response to preoperative treatment: Metastatic response assessment: - Percentage of patients after 6 weeks of preoperative chemotherapy achieving a CR after surgery of metastasis at time of nephrectomy - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after 6 weeks of preoperative chemotherapy + 9 weeks adjuvant chemotherapy. - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after preoperative chemotherapy + 9 weeks adjuvant chemotherapy + metastasectomy - Percentage of patients with remaining metastatic disease after surgery that achieve a CR at week 9 of adjuvant chemotherapy - Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma at the end of adjuvant chemotherapy ± metastasectomy ± RT - Percentage of patients with radiologic complete response (CR) of any metastasis or Very Good Partial Response (VGPR) of lung metastasis of nephroblastoma after 6 weeks of preoperative chemotherapy of patients with remaining metastatic disease after surgery that achieve a CR at week 9 of adjuvant chemotherapy - Primary tumour volume shrinkage after 6 weeks of preoperative chemotherapy - Primary tumour volume after 6 weeks of preoperative chemotherapy - Number of metastases at diagnosis and after preoperative treatment - Maximum diameters of the largest metastases at diagnosis and after preoperative treatment - Histologic & molecular response to preoperative treatment: - Stage distribution of local tumour - Histologic subtype distribution of local tumour (LR, IR, HR) - Histologic subtype distribution of resected nodules/metastsis (LR, IR, HR) - Percentage of blastema and blastemal residual volume in local tumour - Percentage of patients with <10 ml of blastemal residual volume in resected nephroblastoma after 6 weeks of preoperative ch

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Countries

Austria, Belgium, Brazil, Czechia, Czech Republic, Denmark, France, Germany, Greece, Holy See (Vatican City State), Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom

Contacts

Public ContactPD Dr. Rhoikos Furtwängler

SIOP Randomet Studienzentrale

rhoikos.furtwaengler@uks.eu

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026