Short-course Radiotherapy Versus Chemoradiotherapy, Followed by Consolidation Chemotherapy, and Selective Organ Preservation for MRI-defined Intermediate and High-risk Rectal Cancer Patients

• Status: Recruiting
• Trial end date: 2028-10-14
• Target enrollment: 0
• Participant gender: All

Summary

The hereby proposed ACO/ARO/AIO-18.1 randomized trial aims to directly compare the newly established TNT concepts applying either short-course RT according to RAPIDO, or CRT according to CAO/ARO/AIO-04/-12, both followed by consolidation chemotherapy, and surgery or a watch&wait (W&W) approach for patients with clinical complete response (cCR).

The ACO/ARO/AIO-18.1 study incorporates several novel and innovative aspects to further optimize multimodal rectal cancer treatment, partly established by our preceding CAO/ARO/AIO-04 and CAO/ARO/AIO-12 randomized trials: (1) patient selection is based on strict, quality controlled MRI features of intermediate and high-risk characteristics (and, thus, complementary to our ACO/ARO/AIO-18.2 trial in "low-risk" rectal cancer), (2) the CRT regimens incorporates 5-FU/oxaliplatin with doses and intensities shown to be effective and well-tolerated without compromising treatment compliance in CAO/ARO/AIO-04, (3) the sequence of CRT, CT, and surgery/W&W adopts the TNT approach as established by our CAO/ARO/AIO-12 and OPRA trial, (4) surgical stratification allows for W&W management for strictly selected patients with clinical complete response (cCR). Thus, we hypothesize that TNT with 5-FU/oxaliplatin-CRT followed by consolidation chemotherapy may increase organ preservation while maintaining DFS as compared to RAPIDO-like short-course RT followed by consolidation chemotherapy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof. Dr. med. Claus Rödel
• Treatments: Capecitabine; Fluorouracil; Folic Acid; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• 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:

• any cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line, or

• cT3c/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

• cT3 with clear cN+ based on strict MRI-criteria

• cT4 tumors, or

• mrCRM+ (< 1mm), or

• Extramural venous invasion (EMVI+)

• Trans-rectal 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 0-1

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 during treatment and for 6 months after the end of treatment.

• 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).