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

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

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).