A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer – GRECCAR 15 trial protocol

Abstract

Aim: Treatment strategies in locally recurrent rectal cancer (LRRC) are complex and need to be balanced against previous treatments received for the primary rectal cancer.Radiotherapy is an important component of treatment in LRRC. However, there is little high-quality evidence on the role of reirradiation in this cohort. Therefore, the aim of this trial is to assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC.Method: GRECCAR 15 is a prospective, multicentre, open-label, outcome assessorblinded, superiority randomized controlled phase III clinical trial comparing neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone in patients with LRRC previously irradiated for the primary cancer. Adult patients (>18 years old) with a histologically proven resectable LRRC, who have previously received pelvic radiotherapy for their primary rectal cancer at a dose of 25-50.4 Gy, and an Eastern Cooperative Oncology Group performance status of <2 will be eligible to participate. The pelvic reirradiation will consist of conformational intensity-modulated external irradiation, delivering a dose of 30.6 Gy with concomitant chemotherapy using capecitabine.The primary outcome of this trial is the R0 resection rate. Overall, GRECCAR 15 aims to recruit 186 patients to detect an absolute difference of 20% in the R0 resection rate with 80% power and 5% two-sided significance level. Conclusion:The GRECCAR 15 trial is the first, definitive, phase III trial to investigate reirradiation in LRRC. The results of this trial will inform definitively the neoadjuvant treatment strategy in previously irradiated patients and assess whether there is any associated benefit of reirradiation in combination with induction chemotherapy in improving R0 resection rates.

Post-operative complications following dose adaptation of intra-operative electron beam radiation therapy in locally advanced or recurrent rectal cancer

“…Therefore, the confounding effect of induction chemotherapy on perioperative and post-operative complications may be minimal. Prospective data generated from both the trials will provide more insight on induction chemotherapy-related complications [ 23 , 25 ].…”

Locally recurrent rectal cancer: oncological outcomes of neoadjuvant chemoradiotherapy with or without induction chemotherapy

“…While the results of prospective randomized studies 6,7 on the use of ICT in LRRC are awaited, the present study provides data on long-term oncological outcomes of patients with LRRC in two units that had similar management approaches, except with regard to the use of ICT. The principal finding was that there was a trend towards more patients having a pCR in the centre that administered ICT .…”

Locally recurrent rectal cancer: Oncological outcomes for patients with a pathological complete response after neoadjuvant therapy

“…High-quality data on the efficacy of neoadjuvant treatment strategies will be generated by two RCTs that are currently recruiting, the PelvEx II 34 and GRECCAR 15 35 trials. These trials will provide prospective data on the efficacy of neoadjuvant treatment in regard to the achievement of R0 resection, but also with regard to the achievement of a pCR, compliance with therapy, toxicity due to different treatment regimens, and oncological outcomes.…”