Trial document




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  DRKS00021160

Trial Description

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Title

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)

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Trial Acronym

Randomet2017

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URL of the Trial

[---]*

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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.

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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.

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Do you plan to share individual participant data with other researchers?

Yes

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Description 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.

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Organizational Data

  •   DRKS00021160
  •   2020/05/26
  •   [---]*
  •   yes
  •   Approved
  •   169/19, Ethik-Kommission bei der Ärztekammer des Saarlandes
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Secondary IDs

  •   2018-000533-13 
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Health Condition or Problem studied

  •   Metastatic childhood renal tumour
  •   C64 -  Malignant neoplasm of kidney, except renal pelvis
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Interventions/Observational Groups

  •   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
  •   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
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   Yes
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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.

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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

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Countries of Recruitment

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

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Planned
  •   2021/03/01
  •   406
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   3   Months
  •   18   Years
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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

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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

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Addresses

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    • GPOH gGmbH
    • Mr.  Prof. Dr.  Dirk  Reinhardt 
    • Chausseestraße 128/129
    • 10115  Berlin
    • Germany
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    • Zentrum für Forschungsförderung in der Pädiatrie GmbH Pädiatrisches Forschungsnetzwerk gGmbH
    • Ms.  Dr.  Katharina  Jansen 
    • Holsterhauser Platz 2
    • 45147  Essen
    • Germany
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    • Universitätsklinikum des Saarlandes Klinik für Pädiatrische Onkologie und Hämatologie
    • Mr.  PD Dr.  Rhoikos  Furtwängler 
    • Universitätsklinikum Gebäude 9
    • 66421  Homburg
    • Germany
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    • Department of Pediatric Hematology and Oncology La Timone Children’s Hospital
    • Mr.  Dr.  Arnauld  Verschuur 
    • 264, rue Saint Pierre
    • 13364  Marseille Cedex 5
    • France
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    • Universitätsklinikum des Saarlandes Klinik für Pädiatrische Onkologie und Hämatologie
    • Dr.  Yvonne  Braun 
    • Universitätsklinikum Gebäude 9
    • 66421  Homburg
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Krebshilfe
    • Buschstrasse 32
    • 53113  Bonn
    • Germany
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    •   [---]*
    •   [---]*
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Status

  •   Recruiting planned
  •   [---]*
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Trial Publications, Results and other Documents

  •   Votum ff EK
  •   Protokoll V.1.26
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* This entry means the parameter is not applicable or has not been set.