NCT04246684

Short RT Versus RCT,Followed by Chemo.and Organ Preservation for Interm and High-risk Rectal Cancer Patients

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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 702 (actual)
• Sponsor: Prof. Dr. med. Claus Rödel · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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-cCR, or for any locoregional regrowth after initial cCR 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.

Conditions

• Rectal Cancer Stage III

Interventions

Type	Name	Description
DRUG	Oxaliplatin, 85 mg/m2	85 mg/m2,2h-civ, day 22, 36, 50, 64, 78, 92, 106, 120, and 134 of therapy
DRUG	5FU; 2400 mg/m2	2400 mg/m2, 46h-civ, day 22, 36, 50, 64, 78, 92, 106, 120, 134 of therapy for Control arm
DRUG	5FU, 250 mg/m2	250 mg/m2 per day, civ, on day 1-14, day 22-35 of radiotherapy;
DRUG	5FU, 2400 mg/m2	2400 mg/m2,46h-civ, d64, d78, d92, d106, d120, d134 of therapy
DRUG	Oxaliplatin 50 mg/m2	50 mg/m2, 2h-civ, d1, d8, d21, d29 of radiotherapy and
DRUG	Folinic Acid, 400 mg/m2	2h-civ day 22, 36, 50, 64, 78, 92, 106, 120, and 134 of therapyfor Control arm; 400 mg/m2, 2h-civ d 64, d78, d92, d106, d120, d134 of therapy for experimental arm
RADIATION	Radiotherapy control, 5x5 Gy: 25 Gy	Control arm: 5x5 Gy (total: 25 Gy) 5 fractions
DRUG	Capecitabine, 1000 mg/m2	1000 mg/m2 (twice daily) day1-14 every three weeks instead of 5FU optional
DRUG	Oxaliplatin 85 mg/m2	85 mg/m2, 2h-civ, d64, d78, d92, d106, d120, d134 of therapy
RADIATION	radiotherapy experimental, 30 x 1,8 Gy: 54 Gy	30 x 1.8 Gy (total: 54 Gy), 5 fractions per week
DRUG	Capecitabine, 825 mg/m2	825 mg/m2 bid, per os, on day 1-14, 22-35 of RT instead of 5FU optional
DRUG	Oxaliplatin, 130 mg/m2	day1every three weeks (optional)

Timeline

• Start date: 2020-11-05
• Primary completion: 2023-09-15
• Completion: 2028-09-15
• First posted: 2020-01-29
• Last updated: 2024-09-19

Locations

76 sites across 1 country: Germany