BACKGROUND: For patients with low- and intermediate-risk stage II/III rectal cancer, current studies have reached a consensus that preoperative radiotherapy may be dispensed with, and neoadjuvant chemotherapy (NCT) alone might achieve an accepted local control. Our previous phase II study has evidenced that the morphological response of NCT could be better judged at a relatively early stage. Low- and intermediate-risk stage II/III rectal cancer patients could achieve a high rate of tumor shrinkage and downgrade after only 4 cycles of NCT and obvious tumor morphological changes could be observed after 2 cycles of NCT. However, there is still a lack of more detailed stratification and evidence for pathological criteria. The aim of the present study (comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks, COPEC trial) is to determine the pathological tumor regression grade (pTRG) rate of 2 or 4 cycles of NCT in low- and intermediate-risk stage II/III rectal cancer and verify the feasibility of early identification of chemotherapy-insensitive population.
METHODS: This is a multicenter, prospective, non-inferior, randomized controlled trial (RCT) initiated by West China Hospital of Sichuan University and designed to be conducted in fourteen hospitals around China. Eligible patients will be centrally randomized into 2 or 4 cycles of CAPOX in a 1:1 ratio using the central automated randomization system offered by the O-trial online system ( https://plus.o-trial.com/ ) and accept total mesorectal excision after 2 or 4 cycles of CAPOX (oxaliplatin 130 mg/m2, once daily on day 1, every 21 days and capecitabine 1000 mg/m2, twice daily on days 1 to 14, every 21 days). The primary endpoint is the proportion of patients with pathological no-tumor regression (pTRG 3), which is determined postoperatively by each sub-center and verified by the primary center.
CONCLUSIONS: COPEC trial is designed to verify that the preoperative CAPOX chemotherapy for low- and intermediate-risk stage II/III rectal cancer could achieve a good response judgment after 2 cycles and obtain the tumor pathological response rate after 2 cycles of CAPOX. We hope the COPEC trial could help in establishing a consensus standard of low- and intermediate-risk rectal cancer and the early identification of stage II/III rectal patients with low- and intermediate-risk who are poorly responding to NCT.
BACKGROUND: Clinicaltrial.gov NCT04922853. Registered on June 4, 2021.

UNASSIGNED: Immune checkpoint inhibitors (ICIs) have recently been increasingly used in cancer treatment, whereas their clinical application in biliary tract cancer (BTC) patients is uncommon. This study aimed to evaluate the efficacy and safety of ICIs plus capecitabine and oxaliplatin (CAPOX) in the treatment of BTC patients.
UNASSIGNED: This retrospective study reviewed 26 unresectable or advanced BTC patients who received ICIs plus CAPOX. The treatment continued until disease progression, uncontrollable adverse event (AE) occurrence, intolerable toxicity occurrence, or voluntary withdrawal.
UNASSIGNED: The median treatment cycles were 5.5 [interquartile range (IQR): 3.8-8.0]. Complete response, partial response, stable disease, and progressive disease rates were 0.0%, 46.2%, 23.1%, and 30.8%, respectively. Objective response rate (ORR) and disease control rate (DCR) were 46.2% and 69.2%, correspondingly. Regarding survival, the median progression-free survival (PFS) and overall survival (OS) were 6.1 (95% CI: 4.4-7.7) months and 16.5 (95% CI: 5.0-28.0) months; moreover, the 1-year PFS and OS rates were 21.5% and 54.3%, respectively. An Eastern Cooperative Oncology Group (ECOG) score of 1-3 (vs. 0) was associated with declined DCR, PFS, and OS (all p < 0.050). The most common AEs of ICIs plus CAPOX were thrombocytopenia (61.5%), neutropenia (26.9%), and reactive cutaneous capillary endothelial proliferation (RCCEP) (23.1%). Moreover, 13 (50.0%) patients suffered from grade 3-4 AEs, including thrombocytopenia (50.0%), neutropenia (7.7%), liver dysfunction (7.7%), and RCCEP (3.8%). Notably, the majority of AEs were controllable.
UNASSIGNED: ICIs plus CAPOX chemotherapy exhibit a good efficacy and a manageable safety profile in the treatment of patients with unresectable or advanced BTC.

Adjuvant chemotherapy with the CapeOX regimen is now widely used for treating colorectal cancer. However, prior studies have demonstrated better efficacy of pre-operative/neoadjuvant chemotherapy without increase of safety risks.
This multicentre, open-label, parallel-group, randomised, controlled, phase III study aims to compare the efficacy and safety of perioperative CapeOX chemotherapy with the postoperative one for treating patients with locally advanced R0 resectable colon cancers in China. In total 1370 eligible patients will be randomised to: the test group, up to four cycles (every 3 weeks is a cycle, Q3W) of chemotherapy plus radical surgery plus up to four cycles of post-operative chemotherapy; or the control group, radical surgery first, then up to eight cycles of chemotherapy. In each cycle, oxaliplatin will be given at a dose of 130 mg/m2 through continuous IV infusion for 2 hours on the first day. From day 1 to day 14, capecitabine will be taken orally every morning and evening at a dose of 1000mg/m2/d. The primary outcome measure is the 3-year disease free survival. The objective response rate, R0 resection rate, overall survival, as well as the adverse events will also be measured as second endpoints. The study may include two periods. If results of period 1 are not favourable, period 2 will be initiated, recruiting genetically sensitive patients and repeating the same process with period 1.
Informed consent will be required from, and provided, by all subjects. The study protocol has been approved by the independent ethics committee of Shanghai Fudan University Cancer Centre. This study will clearly demonstrate the potential benefit of perioperative chemotherapy with the CapeOX regimen. Results will be shared among all the participating centres, and with policymakers and the academic community to promote the clinical management of colon cancer.
NCT03125980.