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Capecitabine

Oxaliplatin

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w. The TME operation will be given 3-4 weeks after the end of the total neoadjuvant treatment.

The interventions of control group is standard preoperative concurrent chemoradiotherapy. The radiotherapy target areas and dosage are the same as group TNT. During radiotherapy, only oral capecitabine will be delivered and capecitabine dose was 825mg/m2, bid, 5d/w. The TME surgery will be performed 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients will receive another 6 cycles of CAPOX.

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w.

Total neoadjuvant treatment

concurrent chemoradiotherapy

The TME operation will be given after the end of the neoadjuvant treatment.

Patients will receive another 6 cycles of CAPOX after TME.

Adjuvant chemotherapy

Ziqiang Wang

Xin Wang

Ziqiang Wang, MD

Kefeng Ding, MD

Purpose:To compare the efficacy and the safety of total neoadjuvant chemotherapy + TME with standard neoadjuvant concurrent chemoradiotherapy + TME + adjuvant chemotherapy for locally advanced rectal cancer patients with high risk factors of recurrence.

Evaluation indexes: (1) the primary evaluation index: disease-free survival (disease free survival, DFS); (2) the secondary evaluation indexes: pathological complete remission rate (pCR), the 3 year overall survival (overall survival, OS); R0 dissection rate; distant metastasis free survival (DMFS); local recurrence free survival rate (LRRFS); tumor regression grade (TRG, tumor regression grade) and the adverse reaction rate during the chemotherapy, the operation safety index; quality of life; psychological and cognitive effects, assessment of nutritional status.

Safety evaluation indexes: including all adverse events observed during the experiment.

Number of patients: 458 cases Study design: patients will be randomly assigned into the total neoadjuvant treatment group (experimental group, TNT) and neoadjuvant concurrent chemotherapy group (control group, CRT) in the ratio of 1: 1. The patients of experimental group will be given 1 cycle of induction CAPOX (Oxaliplatin 130mg/m2 d1, Capecitabine 1000mg/m2, bid, d1-14) prior to radiotherapy. Then pelvic IMRT/VMAT (50-50.4Gy/25-28f) and two cycles of concurrent chemotherapy (Oxaliplatin 130mg/m2, d1, d 22, Capecitabine 825mg/m2, bid, 5d/w, 25-28d) are performed. And three cycles of consolidation chemotherapy (CAPOX) are delivered after concurrent chemoradiotherapy. Total mesorectal excision (TME) is performed after completion of the whole neoadjuvant treatment. The patients of control group will receive standard concurrent neoadjuvant chemoradiotherapy with capecitabine (825mg/m2, bid, 5d/w) followed by TME 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients are treated with another 6 cycles of CAPOX.

Schedule: Investigators plan to finish the study in 4 years and write the related work within 2 years after the completion of this study.

Total Neoadjuvant Treatment vs. Chemoradiotherapy in Local Advanced Rectal Cancer With High Risk Factors

Total Neoadjuvant Treatment Versus Conventional Neo-chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk Factors: a Multicenter Randomized Phase III Clinical Study.

Time from the completion of the treatment to any recurrences or distant metastases

The rate of complete remission patients to all resected patients

The rate of patients alive 3 years after the completion of treatment

The rate of patients who received R0 dissection to all the patients

Time from the completion of the treatment to any distant metastases

The rate of patients without local recurrence to all the patients

The level of tumor regression under pathological examination

The psychological and cognitive changes of patients after treatment

West China Hospital

Professor

Micronutrients

Hematinics

Irinotecan

Cetuximab

Leucovorin

Fluorouracil

Iron-Dextran Complex

Antineoplastic Agents, Immunological

FOLFOXIRI+Cetuximab regimen:Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h and cetuximab 500mg/m²,all on day 1 of each 2 weeks cycle for 4-6 cycles.

FOLFOXIRI+Cetuximab Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h +Cetuximab 500mg/m²,all on day 1 of each 2 weeks cycle

FOLFOXIRI+Cetuximab regimen

Ming Ye, Master

A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone for local advanced rectal cancer(LARC), but they did not increase the ratio of pathological complete response (pCR) which was associated with improvement of overall survival (OS). On the other hand,some clinical trials show that triple active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) combined with cetuximab for EGFR wild type metastatic colorectal cancer had more effective than double agents.Therefore,a hypothesis is the FOLFOXIRI+Cetuximab as the neoadjuvant chemotherapy regimen might improve the patient's ratio of pCR.

This is a multicenter, phase II trial to assess the efficacy and safety of triplet regimen (FOLFOXIRI) combined with cetuximab for patients with EGFR wild type LARC. After 4 cycles of FOLFOXIRI+cetuximab and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of the multidisciplinary team (MDT),otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625 mg/m²,bid po,d1-5,qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m², bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.

FOLFOXIRI+Cetuximab Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h + Cetuximab 500 mg/m²,all on day 1 of each 2 weeks cycle for 4-6 cycles,

Other Names:

CPT11，CAMPTO Eloxatin Xelod Erbitux

Neoadjuvant Chemotherapy Combined With Cetuximab for EGFR Wild Type Locally Advanced Rectal Cancer

FOLFOXIRI Combined With Cetuximab as a Neoadjuvant Chemotherapy for EGFR Wild Type Locally Advanced Rectal Cancer:A Phase II Study

Common Terminology Criteria for Adverse Events v3.0 (CTCAE)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Total Neoadjuvant Treatment vs. Chemoradiotherapy in Local Advanced Rectal Cancer With High Risk Factors	NCT03177382	Total Neoadjuva... Chemoradiothera... Local Advanced ... High Risk Facto...	Total neoadjuva... concurrent chem... TME Adjuvant chemot...	18 Years - 70 Years	West China Hospital
Neoadjuvant Chemotherapy Combined With Cetuximab for EGFR Wild Type Locally Advanced Rectal Cancer	NCT03391843	Rectal Cancer S...	FOLFOXIRI+Cetux...	18 Years - 75 Years	RenJi Hospital
Neoadjuvant Chemotherapy Combined With Cetuximab for EGFR Wild Type Locally Advanced Rectal Cancer	NCT03391843	Rectal Cancer S...	FOLFOXIRI+Cetux...	18 Years - 75 Years	RenJi Hospital

Spots Global Cancer Trial Database for local advanced rectal cancer