RANDOMET 2017

Patients with metastasized childhood renal tumour

International, Randomized phase 3 clinical trial 

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).

The study includes the first 6 weeks of adjuvant chemotherapy. Thereafter follows a observation of the following chemotherapy, usually over 29 weeks.

• Children <18 years at date of diagnosis and >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

• 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 <3 months or >18 years
• any other medical condition incompatible with the protocol treatment