NCT02363374

Induction Chemotherapy Before or After Preoperative Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer

Induction Chemotherapy Before or After Preoperative Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer: A Randomized Phase II Trial of the German Rectal Cancer Study Group

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 311 (actual)
• Sponsor: Prof. Dr. med. Claus Rödel · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Preoperative 5-FU-based (5-fluorouracil) chemoradiotherapy (CRT), total mesorectal excision surgery, and 4 cycles of adjuvant 5-FU - as established by CAO/ARO/AIO-94 - is at present a standard of care for patients with locally advanced rectal cancer (UICC stage II and III). The phase III German CAO/ARO/AIO-04 trial showed, that the addition of oxaliplatin increased treatment efficacy in terms of early secondary efficacy endpoints (e.g. the pCR-rate). With a median follow-up of 50 months, the primary endpoint of this trial - disease free survival - was significantly improved in the oxaliplatin-containing treatment arm (3-year disease-free survival (DFS) 71.2% versus 75.9%, hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.64-0.98, p=0.03). The hereby proposed randomized phase II trial CAO/ARO/AIO-12 aims at finding novel and innovative aspects of rectal cancer treatment, and will thus provide important information for defining the experimental arm in the upcoming large scale trial of the group. Compared to the current standard, in both study arms, the sequence of the three treatment modalities is modified, placing the chemotherapy block before surgery. The pre-operative sequence of chemotherapy -\> chemoradiotherapy (arm A) has been shown to be feasible with no early tumor progression prior to definitive surgical resection in a small randomized phase II study from Spain. The sequence chemoradiotherapy -\> chemotherapy (arm B) may be beneficial according to response kinetics considerations, and by maintaining a highly effective local treatment in the first place. Both approaches could avoid the problem of major compliance problems with post-operative adjuvant chemotherapy. CAO/ARO/AIO: German Rectal Cancer Study Group

Conditions

• Rectal Neoplasms
• Rectal Cancer Stage II
• Rectal Cancer Stage III

Interventions

Type	Name	Description
DRUG	Induction Chemotherapy arm A	Patients receive three induction chemotherapy cycles, starting on day 1, 15 and 29, consisting of: Folinic acid: 400 mg/sqm, 2h-iv; Oxaliplatin: 100 mg/sqm, 2h-iv; 5-FU: 2400 mg/sqm, 46h-iv After a break of two weeks, radiotherapy starts combined with: 5-FU: 250 mg/sqm per day, iv, on day 43-57, day 64-77 Oxaliplatin: 50 mg/sqm, day 43, 50, 64, and 71
RADIATION	Radiation arm A	Radiotherapy: 28 x 1.8 Gy (total: 50.4 Gy), 5 fractions per week on day 43 -80
RADIATION	Radiation arm B	Radiotherapy: 28 x 1.8 Gy (total: 50.4 Gy), 5 fractions per week on day 1- 38
DRUG	Chemotherapy arm B	chemoradiotherapy is started according to the following schedule: 5-FU: 250 mg/sqm per day, iv, on day 1-14, day 22-35; Oxaliplatin: 50 mg/sqm, day 1, 8, 22, and 29. After a break of two and a half weeks, patients receive three chemotherapy cycles, starting on day 57, 71 and 85, consisting of: Folinic acid: 400 mg/sqm, 2h-iv; Oxaliplatin: 100 mg/sqm, 2h-iv; 5-FU: 2400 mg/sqm, 46h-iv
PROCEDURE	Surgery	Surgery should be performed about 5 (arm B) or 6 (arm A) weeks after the last radiation or chemotherapy, i.e. around day 123

Timeline

• Start date: 2015-03-25
• Primary completion: 2018-09-01
• Completion: 2023-06-16
• First posted: 2015-02-16
• Last updated: 2023-12-04

Locations

20 sites across 1 country: Germany