Neoadjuvant Cetuximab + Chemotherapy Combined With Short-course Radiotherapy

Study Overview
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Brief Summary
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Prospectively Investigate the effectiveness and safety of neoadjuvant cetuximab + chemotherapy (mFOLFOX6) combined with short-course radiotherapy (25Gy/5Fx) for RAS wild-type locally advanced rectal cancer

Official Title
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Efficacy and Safety of Neoadjuvant Cetuximab + Chemotherapy Combined With Short-course Radiotherapy for RAS Wild-type Locally Advanced Rectal Cancer

Conditions
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Neoadjuvant Treatment, Rectal Cancer, Cetuximab, Radiotherapy

Intervention / Treatment
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* Drug: cetuximab+mFOLFOX6
* Radiation: short-course radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A biopsy proven histological diagnosis of rectal adenocarcinoma； An ARMS-PCR proven KRAS, NRAS, PI3KCA and BRAF wild type; No intestinal obstruction, distant metastasis was excluded by CT, MRI or PET / CT; MRI proven T3c-T4, CRM positive, N2, extramural vascular invasion positive or lateral lymph node positive of locally advanced rectal cancer; Age between 18-75 years; ECOG (Eastern US Cooperative Oncology Group) score: 0-1; Has sufficient organ function: Hemopoietic function: hemoglobin ≥ 90 g / L, platelet ≥ 80 g / L × 109 / L, neutrophils ≥ 1.5 × 109/L Liver function: ALT and AST < 2.5 × ULN; Renal function: serum creatinine < 1.5 ULN; Willing to participate and informed consent signed； Exclusion Criteria: Patients with mutations in any of KRAS, NRAS, or BRAF, microsatellite instablility-High; Patients having undergone chemotherapy, radiotherapy or surgery for colorectal cancer; Patients with other uncontrolled malignant tumors (except early-stage basal cell carcinoma or cervical carcinoma in situ) ; Female patients who are pregnant or breastfeeding; Patients with severe heart, liver, or kidney, or neurological or psychiatric disease; Patients with active infection; Poor overall health status, ECOG ≥ 2; Patients with concomitant diseases that seriously endanger the safety of patients or affect the completion of the study in the judgment of the investigator; Known hypersensitivity reactions to any investigational drugs;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cetuximab+mFOLFOX6|cetuximab 500mg/m2 d1 Oxaliplatin 85mg/m2 d1 Calcium Folinate 400mg/m2 d1 5-fluorouridine 400mg/m2 d1 5-fluorouridine 2400mg/m2 46h q2w, 6 cycles|
|Radiation: short-course radiotherapy|25Gy/5Fx short-course radiotherapy between the forth and the fifth cycle of cetuximab+mFOLFOX6|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | Tumor Regression Grade 0-1 | two weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response rate | Refers to the pathological examination of primary tumors and lymph node surgical specimens without residual infiltrating tumor cells (ypT0N0, TRG 0) | two weeks after surgery | 
| 2-year local control rate | Refers to the probability of not finding local recurrence of tumor within 2 years，including anastomotic recurrence confirmed by pathological biopsy, pelvic tumor recurrence confirmed by imaging examination, or suspected pelvic recurrence with CEA exceeding the normal upper limit. | 2 years after enrollment | 
| 2-year metastasis-free rate 2-year distant metastasis free rate | Refers to the probability of no distant metastasis within 2 years | 2 years after enrollment | 
| Overall survival | Refers to the time from the start of treatment to death due to any cause. | 2 years after enrollment | 
| disease-free survival | Refers to the time from the start of treatment to recurrence. | 2 years after enrollment |