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SNCTP000004284 | EUCTR2018-000533-13 | BASEC2020-02881

Eine randomisierte klinische Phase-III-Studie für Kinder und Jugendliche mit einem Nephroblastom im Stadium IV der Arbeitsgruppe für Nierentumore der Internationalen Gesellschaft für Pädiatrische Onkologie (SIOP – RTSG)

Base di dati: BASEC (Importata da 22.11.2024), WHO (Importata da 21.11.2024)
Cambiato: 23 ago 2024, 01:00
Categoria di malattie: Cancro del rene

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Die derzeitige Standardtherapie für Kinder und Jugendliche mit einem Nierentumor mit Metastasen umfasst eine kurze Chemotherapie, eine anschliessende Operation des Nierentumors und eventuell der Metastasen, sowie eine längere Chemotherapie nach der Operation. Einige Patientinnen und Patienten benötigen zusätzlich eine Strahlentherapie. In dieser Studie werden zwei verschiedene Arten der Chemotherapie vor der Operation verglichen. Beide Therapien sind als sehr wirksam bekannt und schon lange bei Kindern und Jugendlichen mit Krebs in Gebrauch. Sie unterscheiden sich allerdings in ihren Nebenwirkungen. Die bisher bekannten Informationen haben gezeigt, dass die derzeitige Standardtherapie gelegentlich schwere, lebensbedrohliche Nebenwirkungen verursacht. Deshalb wird untersucht, ob die Vergleichstherapie, bei der Nebenwirkungen weniger häufig und weniger schwerwiegend auftreten, die Krankheit gleich gut heilen kann wie die Standardtherapie. Das Hauptziel der Studie ist somit, die möglichst wirksamste Behandlung vor der Operation mit den geringsten Nebenwirkungen zu bestimmen.

Malattie studiate(Fonte di dati: BASEC)

Nierentumor mit Metastasen (Stadium IV)

Health conditions (Fonte di dati: WHO)

Stage IV childhood renal tumours;Therapeutic area: Diseases [C] - Cancer [C04]

Malattia rara (Fonte di dati: BASEC)

No

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: BASEC)

In einem ersten Schritt werden die radiologischen Aufnahmen (z.B. Ultraschall und MRI Bilder) der Patientinnen und Patienten zu einer Fachperson geschickt, welche die Existenz von Metastasen außerhalb des Nierentumors prüft. Nachdem die Fachperson die Diagnose bestätigt hat, beginnt die erste Chemotherapie. Die derzeitige Standardtherapie besteht aus den drei Medikamenten Actinomycin D, Vincristin und Doxorubicin und wird kurz ‘VAD’ genannt. Die Vergleichstherapie besteht aus den drei Medikamenten Vincristin, Carboplatin und Etoposid und wird mit ‘VCE’ abgekürzt. Beide Chemotherapien dauern sechs Wochen. Da zurzeit nicht bekannt ist, welche Behandlung für Kinder und Jugendliche mit einem Nierentumor besser ist, entscheidet ein Computer zufällig, welche Patientinnen und Patienten welche Therapie erhalten.
Die weitere Behandlung nach Abschluss der Studientherapie umfasst die Operation des Tumors und eventuell der Metastasen, gefolgt von einer weiteren Chemotherapie und möglicherweise einer Bestrahlung. Die gesamte weitere Behandlung dauert circa 30 Wochen und ist nicht Teil der Studie SIOP Randomet 2017. Den behandelnden Ärztinnen und Ärzten von Studienteilnehmern stehen aber weiter die Erfahrung und das Wissen von Referenzstrahlentherapeuten, Referenzchirurgen und der internationalen Studienleitung zur Verfügung, die Einblick in die Behandlung vieler Kinder mit dieser Erkrankung haben. Zudem werden Proben des operierten Tumors von einem erfahrenen Referenzpathologen im Labor untersucht. Die Ergebnisse dieser Untersuchung können sowohl auf die Wahl der weiteren Chemotherapie, als auch auf die Entscheidung für oder gegen eine Bestrahlung einen wichtigen Einfluss haben.
Nach Abschluss der gesamten Behandlung werden die Patientinnen und Patienten für mindestens zwei Jahre auf Anzeichen eines Wiederauftretens der Krankheit und späte Nebenwirkungen überwacht. In Begleitprojekten soll ferner untersucht werden, ob neue klinische und molekulare Eigenschaften des Tumors entdeckt werden können, die eine weitere Verbesserung der Therapie ermöglichen.

Interventions (Fonte di dati: WHO)


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

Trade Name: Paraplatin
Product Name: Carboplatin
Product Code: L01XA02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Other descriptive name: CARBOPLATIN

Trade Name: Adriamycin
Product Name: Doxorubicin
Pharmaceutical Form:
INN or Proposed INN: DOXORUBICIN
CAS Number: 23214-92-8

Trade Name: VP-16
Product Name: Etoposid
Pharmaceutical Form:
INN or Proposed INN: Etoposid
CAS Number: 33419-42-0
Other descriptive name: ETOPOSIDE

Trade Name: Oncovin
Product Name: Vincristine
Pharmaceutical Form:
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

Erste Diagnose eines Nierentumors mit Metastasen
Patientinnen und Patienten älter als drei Monate und jünger als 18 Jahre zum Zeitpunkt der Diagnose

Criteri di esclusione (Fonte di dati: BASEC)

Zweijährige Nachbeobachtung nach Therapieabschluss nicht möglich
Bereits erhaltene Chemotherapie oder operative Nierenentfernung vor Studienbeginn

Inclusion/Exclusion Criteria (Fonte di dati: WHO)

Gender:
Female: yes
Male: yes

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 (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:
- 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

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000533-13

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2018-000533-13
Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

26 gen 2023

Inserimento del primo partecipante

21 mar 2023

Stato di reclutamento

Not Recruiting

Titolo scientifico (Fonte di dati: WHO)

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)

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional clinical trial of medicinal product

Disegno della sperimentazione (Fonte di dati: WHO)

Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Fase (Fonte di dati: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Punti finali primari (Fonte di dati: WHO)

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

Punti finali secondari (Fonte di dati: WHO)

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 chemotherapy
- Percentage of necrosis in local tumour
- Percentage of patients with complete necrosis in resected nodules
- Percentage of patients with 1q gain being in CR/VGPR in both arms.

- Treatment burden, complications, side effects and toxicity:
- Percentage of patients requiring pulmonary radiotherapy in first line
- Percentage of patients suffering Grade 3 or 4 ALAT or bilirubin increase during preoperative treatment
- Percentage of patients suffering from SOS during preoperative treatment according to EBMT criteria [48]
- Percentage of patients suffering any Grade 4 or grade 5 toxicity during preoperative chemotherapy.
- Overall duration of preoperative treatment per arm as determined as interval D1 ? date of nephrectomy
- Delay in timing of nephrectomy: % of patients with more than 8 weeks since start of preoperative chemotherapy because of toxicity
- Percentage of (peri-)operative complications (haemorrhage, rupture, thromboembolism)
- Outcome:
- Event-free survival at 2 and 5 years for the whole cohort and according to study arm (VAD/VCE) and according to 1qGain
- Overall survival at 2 and 5 years for the whole cohort and according to study arm (VAD/VCE) and according to 1qGain
;Timepoint(s) of evaluation of this end point: after surgery (6 weeks), 9 weeks after initiation of postoperative treatment (if applicable), at the end of overall treatment, 2 years and 5 years (if applicable)

Contatto per informazioni (Fonte di dati: WHO)

Gesellschaft f?r P?diatrische Onkologie und H?matologie gGmbH

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Aarau, Basilea, Bellinzona, Berna, Ginevra, Losanna, Luzern, San Gallo, Zurigo

Paesi di esecuzione (Fonte di dati: WHO)

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

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

Dr. med. Sabine Kroiss
+41 44 266 70 57
sabine.kroiss@kispi.uzh.ch

Contatto per informazioni generali (Fonte di dati: WHO)

PD Dr. Rhoikos Furtw?ngler
Kirrberger Stra?e Geb?ude 9
SIOP Randomet Studienzentrale
rhoikos.furtwaengler@uks.eu

Contatto per informazioni scientifiche (Fonte di dati: WHO)

PD Dr. Rhoikos Furtw?ngler
Kirrberger Stra?e Geb?ude 9
SIOP Randomet Studienzentrale
rhoikos.furtwaengler@uks.eu

Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)

Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)

Kantonale Ethikkommission Zürich

Data di autorizzazione da parte della commissione d’etica

02.03.2021

Altri numeri di identificazione delle sperimentazioni

Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID) (Fonte di dati: BASEC)

2020-02881

Secondary ID (Fonte di dati: WHO)

Randomet2017
2018-000533-13-DE
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