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)
Organizational Data
- DRKS-ID:
- DRKS00021160
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2020-05-26
- Last update in DRKS:
- 2023-10-26
- Registration type:
- Prospective
Acronym/abbreviation of the study
Randomet2017
URL of the study
No Entry
Brief summary in lay language
The Randomet2017 study will be conducted in children and adolescents aged 3 months to 18 years who have a kidney tumor with metastasis(s). In this study, two different combinations of chemotherapeutic agents will be compared. The chemotherapy include either the drugs vincristine, actinomycin D and doxorubicin (VAD) or vincristine, carboplatin and etoposide (VCE). The aim is to find out which of the two therapies is better in terms of effectiveness (probability of cure/ability to make the metastases disappear) and harmfulness (short and long-term side effects). The entire study treatment includes 6 weeks of preoperative chemotherapy. Which therapy (VAD or VCE) is given is decided randomly, like a coin toss.
Brief summary in scientific language
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). Additionally, importance of absolute blastemal volume and the gain of 1q for the prognosis of metastasized nephroblastoma will be investigated.
Health condition or problem studied
- Free text:
- Metastatic childhood renal tumour
- ICD10:
- C64 - Malignant neoplasm of kidney, except renal pelvis
- Healthy volunteers:
- No
Interventions, Observational Groups
- Arm 1:
- Preoperative chemotherapy with vincristine, actinomycin D and doxorubicin. - Actinomycin D, 1 x 45 µg/kg IV day 1 in week 1, 3, 5 - Vincristine, 1 x 1,5 mg/m2 IV day 1 in week 1, 2, 3, 4, 5, 6 - Doxorubicin, 1 x 50 mg/m2 6h IV-Infusion day 1 in week 1, 5 Total duration: 6 weeks
- Arm 2:
- Preoperative chemotherapy with vincristine, carboplatin and etoposide. - Vincristine, 1 x 1,5 mg/m2 IV day 1 in week 1, 2, 3, 4, 5, 6 - Carboplatin, 3 x 200 mg/m2 1h Infusion day 1,2,3 in week 1, 4 - Etoposide, 3 x 100 mg/m2 1h Infusion day 1,2,3 in week 1, 4 Total duration: 6 weeks
Endpoints
- Primary outcome:
- 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.
- Secondary outcome:
- Radiologic response to preoperative treatment: 1. Percentage of patients after 6 weeks of preoperative chemotherapy achieving a CR after surgery of metastasis at time of nephrectomy 2. 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 3. Percentage of patients with remaining metastatic disease after surgery that achieve a CR at week 9 of adjuvant chemotherapy 4. Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after 6 weeks of preoperative chemotherapy + 9 weeks adjuvant chemotherapy. 5. Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma after preoperative chemotherapy + 9 weeks adjuvant chemotherapy + metastasectomy 6. Percentage of patients with complete response +/- VGPR of (pulmonary) metastasis of nephroblastoma at the end of adjuvant chemotherapy ± metastasectomy ± RT 7. Primary tumour volume shrinkage after 6 weeks of preoperative chemotherapy 8. Primary tumour volume after 6 weeks of preoperative chemotherapy 9. Number of metastases at diagnosis and after preoperative treatment 10. Maximum diameters of the largest metastases at diagnosis and after preoperative treatment Treatment burden, complications, side effects and toxicity: 1. Percentage of patients requiring pulmonary radiotherapy in first line 2. Percentage of patients suffering from SOS during preoperative treatment according to EBMT criteria 3. Percentage of patients suffering any Grade 4 or grade 5 (CTCAE) toxicity during preoperative chemotherapy. 4. Overall duration of preoperative treatment per arm as determined as interval D1 – date of nephrectomy 5. Delay in timing of nephrectomy: % of patients with more than 8 weeks since start of preoperative chemotherapy because of toxicity 6. Percentage of (peri-)operative complications (haemorrhage, rupture, thromboembolism) Outcome: 1. Event-free survival at 2 and 5 years for the whole cohort and according to study arm (VAD/VCE) and according to 1qGain 2. Overall survival at 2 and 5 years for the whole cohort and according to study arm (VAD/VCE) and according to 1qGain
Study Design
- Purpose:
- Treatment
- Allocation:
- Randomized controlled study
- Control:
-
- Active control (effective treatment of control group)
- Phase:
- III
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Parallel
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Austria
- Belgium
- Brazil
- Czechia
- Denmark
- France
- Germany
- Greece
- Hungary
- Ireland
- Italy
- Netherlands
- Poland
- Portugal
- Spain
- Sweden
- Switzerland
- United Kingdom
- Vatican City
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- University medical center Leipzig
- University medical center Leipzig
- Medical center Evangelisches Klinikum Bethel Bielefeld
- University medical center Heidelberg
- University medical center Erlangen
- University medical center Freiburg im Breisgau
- University medical center Universitätsklinikum Schleswig-Holstein Campus Lübeck Lübeck
- University medical center Klinikum der LMU Dr. von Haunersches Kinderspital München
- University medical center Frankfurt a.M.
- Medical center Asklepios Klinik St. Augustin Sankt Augustin
- Medical center Städtisches Klinikum Braunschweig gGmbH Braunschweig
- University medical center Greifswald
- Medical center Franz Lust Klinik für Kinder - und Jugendmedizin am städtischen Klinikum Karlsruhe
- Medical center Gesundheit Nordhessen; Klinikum Kassel GmbH Kassel
- University medical center Homburg
- University medical center Bonn
- University medical center Klinikum München Schwabing Kinderklinik der techn. Universität München München
- University medical center Berlin
- Medical center Gesundheit Nord Klinikum Bremen Mitte Bremen
- University medical center Essen
- University medical center Göttingen
- University medical center Mannheim
- University medical center Hamburg
- University medical center Halle Saale
- Medical center Helios Klinikum Erfurt GmbH Erfurt
- University medical center Hannover
- Medical center Kliniken der Stadt Köln gGmbH Kinderkrankenhaus Köln
- University medical center Düsseldorf
- Medical center Diakonie Neuendettelsau KdöR Klinik Hallerwiese/ Cnopfsche Kinderklinik Nürnberg
- University medical center Ulm
- University medical center Köln
- University medical center Tübingen
- Medical center Helios Berlin Buch GmbH Berlin
- University medical center Münster
- University medical center Regensburg
- University medical center Aachen
- University medical center Mainz
- Medical center Klinikum Oldenburg AöR Oldenburg
- University medical center Universitätsklinikum Schleswig-Holstein, Campus Kiel Kiel
- University medical center Würzburg
- Medical center Klinikum Dortmund gGmbH Dortmund
- University medical center Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Giessen
- University medical center Dresden
- University medical center Jena
- Medical center Klinikum Stuttgart - Olgahospital Stuttgart
- Medical center Klinikum Heilbronn GmbH Klinikum am Gesundbrunnen Heilbronn
- University medical center Rostock
- University medical center Augsburg
Recruitment period and number of participants
- Planned study start date:
- 2021-11-30
- Actual study start date:
- 2022-03-04
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 406
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 3 Months
- Maximum Age:
- 18 Years
- Additional Inclusion Criteria:
- - 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. - 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 - 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
Exclusion Criteria
- Patient and/or parental/legal representative(s) denied study participation and randomization - inability to be followed until two years after treatment - primary nephrectomy - histology other than nephroblastoma - other chemotherapy prior to enrolment - 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). - any other medical condition incompatible with the protocol treatment - 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, Nijmegen 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
Addresses
Primary Sponsor
- Address:
- GPOH gGmbHProf. Dr. Dirk ReinhardtChausseestraße 128/12910115 BerlinGermany
- Telephone:
- 0201 723 3784
- Fax:
- 0201 723 5386
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum des Saarlandes KinderklinikProf. Dr. Rhoikos FurtwänglerCampus Gebäude 966421 HomburgGermany
- Telephone:
- 06841 1628025
- Fax:
- 06841 1628024
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uks.eu/de/
Contact for Public Queries
- Address:
- Universitätsklinikum des Saarlandes Klinik für Pädiatrische Onkologie und HämatologieDr. Yvonne BraunUniversitätsklinikum Gebäude 966421 HomburgGermany
- Telephone:
- 06841 1628088
- Fax:
- 06841 1628435
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uks.eu/de/
Principal Investigator
- Address:
- Universitätsklinikum des Saarlandes, KinderklinikProf. Dr. Rhoikos FurtwänglerCampus, Gebäude 966421 HomburgGermany
- Telephone:
- +49 6841 1628025
- Fax:
- +49 6841 1628024
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Other contact for scientific queries
- Address:
- Zentrum für Forschungsförderung in der Pädiatrie GmbH Pädiatrisches Forschungsnetzwerk gGmbHKatharina Waack-BuchholzHolsterhauser Platz 245147 EssenGermany
- Telephone:
- 0201 74 94 96 0
- Fax:
- 0201 8777 54 84
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Deutsche KrebshilfeBuschstrasse 3253113 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission bei der Ärztekammer des SaarlandesFaktoreistr. 466111 SaarbrückenGermany
- Telephone:
- +49-681-4003216
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2019-07-22
- Ethics committee number:
- 169/19
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2019-12-05
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- 2018-000533-13
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- Yes
- IPD Sharing Plan:
- Within the framework of integrated research projects, the data will be made available to other researchers in anonymised form, insofar as this is covered by the data transfer agreement.
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry