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

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.

Conditions

• Rectal Cancer Stage III

Interventions

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)

Sponsors & Collaborators

• Prof. Dr. med. Claus Rödel

  lead OTHER

Principal Investigators

• Claus Roedel, Prof. Dr. · clinic for radiotherapy

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-11-05

Primary Completion

2023-09-15

Completion

2028-09-15

Countries

• Germany

Study Locations