MFOLFOX (neoadjuvant) et XELOX (neoadjuvant) et mFOLFOX (adjuvant) à Cancer rectal - Registre des essais cliniques

Aperçu de l'étude

Statut

Résilié

Les conditions

Cancer rectal

Intervention / Traitement

Description détaillée

Patients with locally advanced rectal cancer are generally treated with preoperative 5-FU- or capecitabine-based chemo-radiotherapy (CRT) and total mesorectal excision (TME) surgery in order to decrease the rate of local failure. In patients with low risk for local failure in the middle third of the rectum (cT3a/b, N-) as determined with quality controlled MRI, the German S3 guidelines and the ESMO clinical practice guidelines state that neoadjuvant radiotherapy may be omitted. However, distant failure rate is still substantial in the range of 20-25% in these patients highlighting the need for more effective systemic treatment.

The hereby proposed ACO/ARO/AIO-18.2 randomized trial incorporates three novel aspects: (1) patient selection relies on strict and quality controlled MRI features and therefore identifies a cohort without imminent need for radiotherapy, (2) the sequence of chemotherapy and surgery is changed in a way that chemotherapy is administered preoperatively to increase the rate of patients treated with chemotherapy, and (3) three months of neoadjuvant FOLFOX or XELOX (instead of up to 6 months adjuvant chemotherapy) are used as a sole perioperative treatment in order to administer effective doses of the presumably most effective perioperative treatment at an early time point during the course of disease.

Thus, patients with locally advanced rectal cancer but low risk for local failure (cT1/2N+ in all thirds of the rectum, cT3a/b N- in the middle third, and cT3-4 Nany in the upper third) will be included and randomized between three months of neoadjuvant FOLFOX/XELOX in Arm A and primary resection of the tumor followed by risk (i.e. stage) adapted chemotherapy in Arm B.

Type d'étude

Interventionnel

Inscription (Réel)

215

Phase

Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

Allemagne
- - Mannheim, Allemagne, 68167
    - Unversity Hospital Mannheim

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localised 0 - 16 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower, middle and upper third of the rectum), depending on MRI-defined inclusion criteria (see below).
Staging requirements: High-resolution magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
Transrectal endoscopic ultrasound (EUS) is used to help discriminate between T1/2 and early T3 tumors.
MRI-defined inclusion criteria:

i. Lower third (0-6 cm):
- cT1/2 with clear cN+ based on defined MRI criteria or T3a-b (i.e. maximum infiltration into the perirectal fat of 5mm), provided CRM > 2mm and EMVI-** ii. Middle third (≥ 6-12 cm):
- cT1/2 with clear cN+ provided CRM- and EMVI-**
- cT3 irrespective of the depth of invasion into the perirectal fat, provided no evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on MRI (i.e. CRM > 2 mm), N0 or N1, EMVI-** iii. Upper third (≥ 12-16 cm):
- cT1/2 with clear cN+, irrespective of CRM and EMVI
- any cT3-4 irrespective of nodal status, CRM and EMVI.
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:
Leukocytes ≥ 3.000/mm³, ANC ≥ 2.000/mm³, platelets ≥ 100.000/mm³, Hb > 9 g/dl
Serum creatinine ≤ 1.5 x upper limit of normal
Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal.
QTc interval (Bazett**) ≤ 440 ms
Informed consent of the patient.

"**" Formula for QTc interval calculation (Bazett): QTc= ((QT) ̅" (ms)" )/√(RR (sec))= ((QT) ̅" (ms)" )/√(60/(frequency (1/min)))

Exclusion Criteria:

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 during treatment and for 6 months (male or female) after the end of treatment Male patients treated with Oxaliplatin should take legal advice concerning sperm conservation before start of therapy and should additionally use a condom during treatment period. Their female partner of childbearing potential should also use an appropriate contraceptive measure.
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.
Chronic diarrhea (> grade 1 according NCI CTCAE).
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 or hypersensitivity on study medication or to any of the other excipients.
Evidence of peripheral sensory neuropathy > grade 1 according to CTCAE version 5.0 (see appendix).
Severe kidney dysfunction (creatinine clearance < 30 ml/min).
Recent or concurrent treatment with brivudine.
Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.
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).

"***"highly effective (i.e. failure rate of <1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Objectif principal: Traitement
Répartition: Randomisé
Modèle interventionnel: Affectation parallèle
Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras Groupe de participants / Bras Un groupe ou un sous-groupe de participants à un essai clinique qui reçoit une intervention/un traitement spécifique, ou aucune intervention, selon le protocole de l'essai.	Intervention / Traitement Intervention / Traitement Processus ou action faisant l'objet d'une étude clinique. Les interventions comprennent les médicaments, les dispositifs médicaux, les procédures, les vaccins et d'autres produits expérimentaux ou déjà disponibles. Les interventions peuvent également inclure des approches non invasives, telles que l'éducation ou la modification du régime alimentaire et de l'exercice.
Expérimental: A (experimental arm) The experimental arm A starts with 6 cycles of mFOLFOX or 4 cycles of XELOX. Surgery is scheduled four or six weeks after day 1 of the last mFOLFOX or XELOX cycle, respectively. No postoperative chemotherapy is planned	Médicament: mFOLFOX (neoadjuvant) neoadjuvant application Folinic acid: 400 mg/m2, 2h i.v., on day 1 Oxaliplatin: 85 mg/m2, 2-6h i.v., on day 1 5-FU: 2400 mg/m2, 46-48h i.v., on day 1. Cycles are repeated on day 15. A total of 6 cycles are administered. Autres noms: Acide folinique, Oxaliplatine, 5-FU Médicament: XELOX (neoadjuvant) neoadjuvant application Capecitabine: 1,000 mg/m2 bid, po, on days 1-14 Oxaliplatin: 130 mg/m2, 2-6h i.v. day 1 Cycles are repeated on day 22. A total of 4 cycles are administered. Autres noms: Capécitabine, Oxaliplatine
Comparateur actif: B (control arm) In the standard arm B, patients undergo surgical resection of the primary tumor followed by stage- (risk-)adapted adjuvant chemotherapy 4-8 weeks after surgery according to recommendations of the S3 guidelines in analogy to colon cancer. Details of the recommended protocols are provided in the protocol.	Médicament: mFOLFOX (adjuvant) adjuvant application Folinic acid: 400 mg/m2, 2h i.v., on day 1 Oxaliplatin: 85 mg/m2, 2-6h i.v., on day 1 5-FU: 2400 mg/m2, 46-48h i.v., on day 1. Cycles are repeated on day 15. A total of 6 cycles are administered. Autres noms: Acide folinique, Oxaliplatine, 5-FU Médicament: XELOX (adjuvant) adjuvant application Capecitabine: 1,000 mg/m2 bid, po, on days 1-14 Oxaliplatin: 130 mg/m2, 2-6h i.v. day 1 Cycles are repeated on day 22. A total of 4 cycles are administered. Autres noms: Capécitabine, Oxaliplatine Médicament: Capecitabine (adjuvant) adjuvant application Capecitabine: 1,250 mg/m2 bid, po, on days 1-14 Cycles are repeated on day 22. A total of 8 cycles are administered. Autres noms: Capécitabine Médicament: infusional 5-FU/FA "AIO" regimen (adjuvant) adjuvant application Folinic acid 2h i.v. 500 mg/m² 5-FU 2,600mg/m² (24h infusion) Days 1, 8, 15, 22, 29, 36; cycle is repeated day 57 (representing one cycle); a total of 3 cycles should be administered. Autres noms: 5-FU, acide folinique Médicament: infusional 5-FU/FA "de Gramont" (adjuvant) adjuvant application Folinic acid 2h i.v. 200 mg/m² days 1 and 2 5-FU 400mg/m² bolus followed by 600mg/m² 22h infusion days 1 and 2 The cycle is repeated day 15; a total of 12 cycles should be administered. Autres noms: 5-FU, acide folinique

Groupe de participants / Bras

Intervention / Traitement

Expérimental: A (experimental arm)

The experimental arm A starts with 6 cycles of mFOLFOX or 4 cycles of XELOX. Surgery is scheduled four or six weeks after day 1 of the last mFOLFOX or XELOX cycle, respectively. No postoperative chemotherapy is planned

Médicament: mFOLFOX (neoadjuvant)

neoadjuvant application Folinic acid: 400 mg/m2, 2h i.v., on day 1 Oxaliplatin: 85 mg/m2, 2-6h i.v., on day 1 5-FU: 2400 mg/m2, 46-48h i.v., on day 1. Cycles are repeated on day 15. A total of 6 cycles are administered.

Autres noms:

Acide folinique, Oxaliplatine, 5-FU

Médicament: XELOX (neoadjuvant)

neoadjuvant application Capecitabine: 1,000 mg/m2 bid, po, on days 1-14 Oxaliplatin: 130 mg/m2, 2-6h i.v. day 1 Cycles are repeated on day 22. A total of 4 cycles are administered.

Autres noms:

Capécitabine, Oxaliplatine

Comparateur actif: B (control arm)

In the standard arm B, patients undergo surgical resection of the primary tumor followed by stage- (risk-)adapted adjuvant chemotherapy 4-8 weeks after surgery according to recommendations of the S3 guidelines in analogy to colon cancer. Details of the recommended protocols are provided in the protocol.

Médicament: mFOLFOX (adjuvant)

adjuvant application Folinic acid: 400 mg/m2, 2h i.v., on day 1 Oxaliplatin: 85 mg/m2, 2-6h i.v., on day 1 5-FU: 2400 mg/m2, 46-48h i.v., on day 1. Cycles are repeated on day 15. A total of 6 cycles are administered.

Autres noms:

Acide folinique, Oxaliplatine, 5-FU

Médicament: XELOX (adjuvant)

adjuvant application Capecitabine: 1,000 mg/m2 bid, po, on days 1-14 Oxaliplatin: 130 mg/m2, 2-6h i.v. day 1 Cycles are repeated on day 22. A total of 4 cycles are administered.

Autres noms:

Capécitabine, Oxaliplatine

Médicament: Capecitabine (adjuvant)

adjuvant application Capecitabine: 1,250 mg/m2 bid, po, on days 1-14 Cycles are repeated on day 22. A total of 8 cycles are administered.

Autres noms:

Capécitabine

Médicament: infusional 5-FU/FA "AIO" regimen (adjuvant)

adjuvant application Folinic acid 2h i.v. 500 mg/m² 5-FU 2,600mg/m² (24h infusion) Days 1, 8, 15, 22, 29, 36; cycle is repeated day 57 (representing one cycle); a total of 3 cycles should be administered.

Autres noms:

5-FU, acide folinique

Médicament: infusional 5-FU/FA "de Gramont" (adjuvant)

adjuvant application Folinic acid 2h i.v. 200 mg/m² days 1 and 2 5-FU 400mg/m² bolus followed by 600mg/m² 22h infusion days 1 and 2 The cycle is repeated day 15; a total of 12 cycles should be administered.

Autres noms:

5-FU, acide folinique

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats	Description de la mesure	Délai
disease-free survival Délai: up to 3 years	time from randomisation to one of the following events: no surgery or non-radical (R2) surgery of the primary tumour, locoregional recurrence after R0/1 resection of the primary tumour, second primary colorectal or other cancer, metastatic disease or progression, or death from any cause, whichever occurred first.	up to 3 years

Mesures de résultats secondaires

Mesure des résultats	Description de la mesure	Délai
Acute and late toxicity Délai: From date of informed consent until the End of Treatment or 30 days after the last dose of study treatment	assessment of acute and late toxicity according to NCI CTCAE version 5.0	From date of informed consent until the End of Treatment or 30 days after the last dose of study treatment
Compliance (completion rate) of chemotherapy Délai: From date of randomization until end of chemotherapy, approx. 12 (arm A) respectively up to 34 (arm B) weeks after randomization	Rate of completion of administered chemotherapy	From date of randomization until end of chemotherapy, approx. 12 (arm A) respectively up to 34 (arm B) weeks after randomization
Surgical morbidity and complications Délai: After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization	Surgical morbidity and complications if surgery is performed and events occur	After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization
Pathological UICC-staging, including pCR (ypT0N0) rate Délai: After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization	Pathological staging according UICC criteria, including detailed information about pathologically assessed complete response rate (ypT0N0)	After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization
R0 resection rate, Negative circumferential resection rate (CRM > 1mm) Délai: After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization	defined as microscopically margin negative resection with no gross or microscopic tumor remains in the area of the primary tumor and/or samples regional lymph nodes based on evaluation by the local pathologist	After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization
Tumor regression grading according to Dworak in the experimental arm Délai: After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization	Grading of tumor regression according to Dworak in the experimental arm	After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization
Rate of sphincter-sparing surgery Délai: After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization	Rate of sphincter-sparing surgery if surgery is performed	After surgery, approx. 2 (arm B) respectively 20 (arm A) weeks after randomization
Rate of W&W with or without local regrowth Délai: Up to 5 years after end of treatment	Number of performed watch&wait approaches with or without local regrowth compared to planned and performed surgery	Up to 5 years after end of treatment
Cumulative incidence of local and distant recurrences Délai: Up to 5 years after end of treatment	Total number of local and distant recurrences, if they occur	Up to 5 years after end of treatment
Overall survival Délai: Up to at least 3 years and until 5 years	Overall survival is defined as the time interval between the date of randomization and the date of death of any cause. Patients who are still alive when last traced will be censored at the date of last follow-up	Up to at least 3 years and until 5 years
Patient reported outcome: Quality of life according to questionnaire EORTC-QLQ-C30 Délai: From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months	Quality of life scores according to validated questionnaires EORTC-QLQ-C30, based on treatment arm, and surgical procedures. 30 questions; score values from 1 (not at all) to 4 (very much) respectively from 1 (very poor) to 7 (excellent). Score outcome depends on score type.	From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months
Patient reported outcome: Quality of life according to questionnaire EORTC-QLQ-CR29 Délai: From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months	Quality of life scores according to validated questionnaires EORTC-QLQ-CR29, based on treatment arm, and surgical procedures. 29 questions; score values from 1 (not at all) to 4 (very much). Score outcome depends on score type.	From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months
Patient reported outcome: Functional outcome according to Wexner score Délai: From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months	Functional score according to validated Wexner score, based on treatment arm, and surgical procedures. 5 questions; five score values from "never" to "1 per day or more often". The more often the worse the outcome.	From date of randomization until the date of first documented progression or date of death from any cause, whichever occured first, assessed up to approximately 68 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Ralf Hofheinz

Collaborateurs

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Deutsche Krebshilfe e.V., Bonn (Germany)

German Rectal Cancer Study Group

Les enquêteurs

Chercheur principal: Ralf-Dieter Hofheinz, Prof. Dr., Universitätsmedizin Mannheim

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

30 septembre 2020

Achèvement primaire (Réel)

31 juillet 2026

Achèvement de l'étude (Réel)

31 juillet 2026

Dates d'inscription aux études

Première soumission

28 juillet 2020

Première soumission répondant aux critères de contrôle qualité

28 juillet 2020

Première publication (Réel)

31 juillet 2020

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Cancer rectal

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

ACO/ARO/AIO-18.2
2018 (Subvention/contrat des NIH des États-Unis)
2018-001356-35 (Numéro EudraCT)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

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Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

FOLFOX préopératoire versus chimiothérapie postopératoire adaptée au risque chez les patients atteints d'un cancer du rectum localement avancé

FOLFOX préopératoire versus chimiothérapie postopératoire adaptée au risque chez les patients atteints d'un cancer rectal localement avancé et à faible risque d'échec local : un essai randomisé de phase III du groupe d'étude allemand sur le cancer rectal

Aperçu de l'étude

Statut

Les conditions

Intervention / Traitement

Description détaillée

Type d'étude

Inscription (Réel)

Phase

Contacts et emplacements

Lieux d'étude

Critères de participation

Critère d'éligibilité

Âges éligibles pour étudier

Accepte les volontaires sains

Sexes éligibles pour l'étude

La description

Plan d'étude

Comment l'étude est-elle conçue ?

Détails de conception

Nombre de bras

Armes et Interventions

Groupe de participants / Bras

Intervention / Traitement

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats

Description de la mesure

Délai

Mesures de résultats secondaires

Mesure des résultats

Description de la mesure

Délai

Collaborateurs et enquêteurs

Parrainer

Collaborateurs

Les enquêteurs

Dates d'enregistrement des études

Dates principales de l'étude

Début de l'étude (Réel)

Achèvement primaire (Réel)

Achèvement de l'étude (Réel)

Dates d'inscription aux études

Première soumission

Première soumission répondant aux critères de contrôle qualité

Première publication (Réel)

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

Dernière mise à jour soumise répondant aux critères de contrôle qualité

Dernière vérification

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Étudie un produit d'appareil réglementé par la FDA américaine