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SNCTP000004782 | EUCTR2018-000876-14 | BASEC2021-01686

Kurzzeit-Radiotherapie versus Radiochemotherapie, gefolgt von konsolidierender Chemotherapie und selektivem Organerhalt für Patienten mit MRT-definierten intermediären und Hoch-Risiko-Rektumkarzinom Eine randomisierte Phase III-Studie der German Rectal Cancer Group ACO/ARO/AIO-18.1

Base di dati: BASEC (Importata da 29.03.2024), WHO (Importata da 29.03.2024)
Cambiato: 23 dic 2023, 16:58
Categoria di malattie: Cancro del colon-retto

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Das lokal fortgeschrittene Rektumkarzinom (Enddarmkrebs) wird üblicherweise mit einer Kombination aus Bestrahlung und Chemotherapie (Radiochemotherapie) behandelt und anschliessend der Tumor mittels Operation entfernt. Häufig wird nach der Operation eine Chemotherapie angeschlossen um das Rückfallrisiko weiter zu senken. Diese Therapie wird gemäss neuen Erkenntnissen zunehmend auch bereits vor der Operation durchgeführt. Unklar ist bisher, welche Art der Bestrahlung am wirkungsvollsten ist und ob es bei einem sehr guten Ansprechen, wirklich in jedem Fall eine Operation braucht. Deshalb wird in dieser Studie eine Kurzzeit-Radiotherapie (Standarttherapie) mit einer Radiochemotherapie über 5-6 Wochen (neuerer Ansatz) verglichen. Alle Patienten erhalten anschliessend die übliche Chemotherapie für 4.5 respektive 3 Monate. Diese beiden untersuchten Varianten haben sich in den Vorläuferstudien als gut verträglich und bezüglich des Ansprechens als vielversprechend erwiesen. Unser Ziel ist es, die Behandlungsergebnisse der Standardtherapie bezüglich Wirksamkeit und Verträglichkeit sowie Aspekten der Lebensqualität und der Möglichkeit des Organerhalts (Verzicht auf Operation), weiter zu verbessern. Wir wollen daher in unserer Studie nach Abschluss der Bestrahlung und Chemotherapie vor der eigentlich geplanten Operation prüfen, ob der Tumor bei Ihnen überhaupt noch nachweisbar ist. Eine solche sogenannte „pathologische Komplettremission“ wird bei ca. 25% der Patienten beschrieben. Wird bei diesen Untersuchungen übereinstimmend festgestellt, dass der Tumor ist nicht mehr nachweisbar ist, kann in unserer Studie auf die Operation verzichtet werden. Stattdessen werden Patienten mit einer solchen klinischen Komplettremission in ein engmaschiges Nachsorge-Protokoll aufgenommen (sog. „Watch&Wait-Strategie“), im Rahmen dessen regelmäßig überprüft wird, ob der Tumor lokal weiterhin vollständig geheilt bleibt. Nur im Falle eines erneuten lokalen Tumorwachstums erfolgt dann die Operation.

Malattie studiate(Fonte di dati: BASEC)

Lokal fortgeschrittenes Rektumkarzinom (Enddarmkrebs)

Health conditions (Fonte di dati: WHO)

Locally advanced rectal cancer (UICC stage II and III)
MedDRA version: 21.0Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);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 dieser Studie wird untersucht, ob eine neuartige Kombination und Sequenz der Radiochemotherapie hinsichtlich des Tumoransprechens und der langfristigen Heilungsraten genauso wirksam oder sogar effektiver ist als die Standard-Therapie im Kontrollarm mit einer kurzzeitigen Radiotherapie. (Superiority design)
Der experimentelle Arm besteht aus einer Radiochemotherapie (RCT) mit 5-Fluorouracil oder Capecitabin über etwa 5-6 Wochen, der sich eine weiterführende Chemotherapie (mit Fluorouracil/Capecitabin und Oxaliplatin) über 3 Monaten anschliesst.
Der Kontrollarm ist eine Kurzzeit-Radiotherapie an 5 aufeinanderfolgen Tagen. Nach 1,5 bis 2,5 Wochen folgt eine Chemotherapie (mit Fluorouracil/Capecitabin und Oxaliplatin) über 4,5 Monate.
2-4 Wochen nach Ende der Chemotherapie erfolgt für alle Studienteilnemer*innen eine Beurteilung des Tumoransprechens mittels Enddarmspiegelung und Bildgebung (MRI) und Besprechung einer nachfolgenden operativen Entfernung des Tumors und des umliegenden Gewebes (z.B. Lymphknoten).
Für beide Behandlungsgruppen gilt: Sollte der Tumor gemäss den erwähnten Untersuchungen so gut angesprochen haben, kein Tumor mehr nachweisbar ist (klinischen Komplettremission), wird auf eine radikale Operation zugunsten einer engmaschigeren Nachsorge (Watch&Wait-Strategie) verzichtet. Dieses Vorgehen ist prinzipiell in beiden Studienarmen für Patienten erlaubt, die eine solche klinische Komplettremission aufweisen. Wichtig ist dabei allerdings Ihre Bereitschaft zu enger und regelmässiger Nachsorge innerhalb unserer Studie. Die Nachsorge beinhaltet Enddarmspiegelungen und Bildgebung (MRT) alle 3 Monaten in den ersten 2 Jahren.

Interventions (Fonte di dati: WHO)


Product Name: 5-fluorouracil
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FLUOROURACIL
Other descriptive name: FLUOROURACIL

Product Name: Oxaliplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3

Product Name: Capecitabine
Pharmaceutical Form: Tablet
INN or Proposed INN: CAPECITABINE
Other descriptive name: CAPECITABINE

Product Name: folinic acid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FOLINIC ACID
Other descriptive name: FOLINIC ACID

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

- Männer und Frauen mit histologisch bestätigtem Befund eines lokal fortgeschrittenem Rektumkarzinoms, welches sich im unteren bis mittleren Drittel des Enddarms befindet.
- ≤ 18 Jahre
- Einverständiserklärung des Patienten

Criteri di esclusione (Fonte di dati: BASEC)

- Entfernte Ableger (Metastasen)
- vorgängige Behandlund des Enddarmkrebs
- andere begleitende Krebsbehandlungen

Inclusion/Exclusion Criteria (Fonte di dati: WHO)

Inclusion criteria:
•Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localised 0 – 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum).
•Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
•MRI-defined inclusion criteria: presence of at least one of the following high-risk conditions:
oany cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line, or
ocT3c/d in the middle third of the rectum (= 6-12 cm) with MRI evidence of extramural tumor spread into the mesorectal fat of more than 5 mm (>cT3b), or
ocT3 with clear cN+ based on strict MRI-criteria (see appendix)
ocT4 tumors, or
oTany middle/low third of rectum with clear MRI criteria for N+
omrCRM+ (= 1mm), or
oExtramural venous invasion (EMVI+).
•Transrectal endoscopic ultrasound (EUS) is additionally used when MRI is not definitive to exclude early cT1/T2 disease in the lower third of the rectum or early cT3a/b tumors in the middle third of the rectum.
•Spiral-CT of the abdomen and chest to exclude distant metastases.
•Aged at least 18 years. No upper age limit.
•WHO/ECOG Performance Status =1.
•Adequate haematological, hepatic, renal and metabolic function parameters:
oLeukocytes = 3.000/mm3, ANC = 1.500/mm3, platelets = 100.000/mm3, Hb > 9 g/dl
oSerum creatinine = 1.5 x upper limit of normal
oBilirubin = 2.0 mg/dl, SGOT-SGPT, and AP = 3 x upper limit of normal.
•Informed consent of the patient
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 102

Exclusion criteria:
•Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy.
•Distant metastases (to be excluded by CT scan of the thorax and abdomen).
•Prior antineoplastic therapy for rectal cancer.
•Prior radiotherapy of the pelvic region.
•Major surgery within the last 4 weeks prior to inclusion.
•Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
•Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
•On-treatment participation in a clinical study in the period 30 days prior to inclusion.
•Previous or current drug abuse.
•Other concomitant antineoplastic therapy.
•Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.
•Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = 6 months before enrolment.
•Prior or concurrent malignancy = 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free.
•Known allergic reactions on study medication.
•Known dihydropyrimidine dehydrogenase deficiency.
•Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000876-14

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

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2018-000876-14
Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

8 ott 2019

Inserimento del primo partecipante

21 gen 2020

Stato di reclutamento

Authorised-recruitment may be ongoing or finished

Titolo scientifico (Fonte di dati: WHO)

ACO/ARO/AIO-18.1: Short-course radiotherapy versus chemoradiotherapy, followed by consolidation chemotherapy, and selective organ preservation for MRI-defined intermediate and high-risk rectal cancer patientsA randomized phase III trial of the German Rectal Cancer Study Group - ACO/ARO/AIO-18.1

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: no
Placebo: no
Other: yes
Other specify the comparator: Preoperative oxaliplatin-based CRT and consolidation CT versus fluorouracil-based CRT
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: The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma. Accordingly, the primary endpoint, organ preservation, will not be reached if any of the following occurs: (1) death, (2) any major surgery other than local excision (R0) performed after randomization, during TNT, at re-staging scheduled 22-24 weeks after start of TNT due to clinical non-complete response, or for any locoregional regrowth after initial clinical complete response requiring salvage-TME, (3) any locoregional regrowth not amenable to salvage surgery, or (4) any stoma (non-re-converted protective stoma within 6 months after completion of TNT, or any stoma needed for toxicity or poor function), whichever occurs first. We hypothesized that the 3-year organ preservation rate will improve from 30% in the control arm to 40% in the investigational arm (hazard ratio of 0.76). ;Secondary Objective: •Disease-free survival
•Rate of clinical complete response after TNT
•Rate of immediate TME after TNT
•Cumulative incidence of locoregional regrowth after cCR
•Rate of salvage surgery (LE/TME with or without APR/stoma) after locoregional regrowth
•Cumulative incidence of local recurrence after (salvage) surgery
•Postoperative complications of (salvage) surgery
•Rate of sphincter-sparing (salvage) surgery
•Pathological TNM-staging
•R0 resection rate; negative circumferential resection rate
•Tumor regression grading according to Dworak
•Neoadjuvant rectal score
•Quality of TME according to MERCURY
•Acute and late toxicity assessment according to NCI CTCAE V.5.0)
•Quality of life and functional outcome based on treatment arm and surgical procedures/organ preservation
•Cumulative incidence of distant metastases
•Overall survival
;Primary end point(s): The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma. Accordingly, the primary endpoint, organ preservation, will not be reached if any of the following occurs: (1) death, (2) any major surgery other than local excision (R0) performed after randomization, during TNT, at re-staging scheduled 22-24 weeks after start of TNT due to clinical non-complete response, or for any locoregional regrowth after initial clinical complete response requiring salvage-TME, (3) any locoregional regrowth not amenable to salvage surgery, or (4) any stoma (non-re-converted protective stoma within 6 months after completion of TNT, or any stoma needed for toxicity or poor function), whichever occurs first. We hypothesized that the 3-year organ preservation rate will improve from 30% in the control arm to 40% in the investigational arm (hazard ratio of 0.76). With a power of 90% and a two-sided type I error of 5%, the sample size required to obtain a statistically significant difference is 702 patients (564 events) in total.;Timepoint(s) of evaluation of this end point: End of therapy

Punti finali secondari (Fonte di dati: WHO)

Secondary end point(s): •Disease-free survival
•Rate of clinical complete response after TNT
•Rate of immediate TME after TNT
•Cumulative incidence of locoregional regrowth after cCR
•Rate of salvage surgery (LE/TME with or without APR/stoma) after locoregional regrowth
•Cumulative incidence of local recurrence after (salvage) surgery
•Postoperative complications of (salvage) surgery
•Rate of sphincter-sparing (salvage) surgery
•Pathological TNM-staging
•R0 resection rate; negative circumferential resection rate
•Tumor regression grading according to Dworak
•Neoadjuvant rectal score
•Quality of TME according to MERCURY
•Acute and late toxicity assessment according to NCI CTCAE V.5.0)
•Quality of life and functional outcome based on treatment arm and surgical procedures/organ preservation
•Cumulative incidence of distant metastases
•Overall survival
•Translational / biomarker studies;Timepoint(s) of evaluation of this end point: after 3 year follow up

Contatto per informazioni (Fonte di dati: WHO)

German Cancer Aid

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ACO/ARO/AIO-18.1: Short-course radiotherapy versus chemoradiotherapy, followed by consolidation chemotherapy, and selective organ preservation for MRI-defined intermediate and high-risk rectal cancer patientsA randomized phase III trial of the German Rectal Cancer Study Group

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)

Basilea

Paesi di esecuzione (Fonte di dati: WHO)

È possibile che la Svizzera non appaia ancora come paese di esecuzione perché non è ancora stata registrata nel registro primario dell’OMS.
Germany

Contatto per maggiori informazioni sulla sperimentazione

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

Wolfgang Harms
+41616858585
wolfgang.harms@claraspital.ch

Contatto per informazioni generali (Fonte di dati: WHO)

Atefeh Nateghian
Theodor-Stern-Kai 7
University Hospital Frankfurt, Goethe University
004906963014655
studien-strahlen@kgu.de

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Atefeh Nateghian
Theodor-Stern-Kai 7
University Hospital Frankfurt, Goethe University
004906963014655
studien-strahlen@kgu.de

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)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Data di autorizzazione da parte della commissione d’etica

31.01.2022

Altri numeri di identificazione delle sperimentazioni

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

2021-01686

Secondary ID (Fonte di dati: WHO)

ACO/ARO/AIO-18.1
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