Induction Chemotherapy for MRF-negative, Moderate-risk, Resectable Middle and Low Rectal Cancer

Study Overview
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Brief Summary
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This study is designed to test the Safety and efficacy of induction and individualized neoadjuvant chemotherapy based on oxaliplatin combined with fluorouracil for MRF-negative, moderate-risk and initially resectable middle and low rectal cancer.

Detailed Description
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Preoperative chemoradiation has become standard treatment for stage 2/3 rectal cancer. But for moderate-risk rectal cancer patients, whether neoadjuvant chemotherapy followed with total mesorectal excision is adequate for local control is still unknown. The necessity of preoperative radiotherapy for these patients needs further exploration. This study is a single-arm, single-center, prospective, phase II clinical study. It is designed to test the efficacy and safety of neoadjuvant chemotherapy for MRF-negative, moderate-risk and initially resectable middle and low rectal cancer. In this study, patients with MRI defined moderate-risk rectal cancer will receive a three-month neoadjuvant chemotherapy based on Oxaliplatin combined with Fluorouracil(CapeOX,SOX,mFOLFOX6,etc.) and Total mesorectal excision. Primary Endpoint is pCR rate.Secondary endpoint concludes toxic reactions of neoadjuvant chemotherapy, Incidence of surgical complications and three-year disease-free survival (DFS). This study is designed to recruit 119 patients in all.

Official Title
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Safety and Efficacy of Induction and Individualized Neoadjuvant Chemotherapy Based on Oxaliplatin Combined With Fluorouracil for MRF-negative, Moderate-risk and Initially Resectable Middle and Low Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Oxaliplatin and capecitabine
* Procedure: Total Mesorectal Excision


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Age ≥18 years and ≤80 years ECOG Performance status 0-1 Histologically confirmed diagnosis of adenocarcinoma of the rectum The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12cm based on sigmoidoscopy; Clinical Stage based on MRI mrMRF(-) T3c/T3d/T4a, anyN, or T3bN+ No evidence of distant metastases No prior pelvic radiation therapy No prior chemotherapy or surgery for rectal cancer No active infections requiring systemic antibiotic treatment ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN. Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Exclusion Criteria: • Recurrent rectal cancer Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs and an en-bloc resection will not achieve negative margins. The pathological grade was Grade 4, i.e. mucus, signet ring or undifferentiated cancer. Creatinine level greater than 1.5 times the upper limit of normal. Patients who have received prior pelvic radiotherapy. Patients who are unable to undergo an MRI. Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer. Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA. Other Anticancer or Experimental Therapy. Women who are pregnant or breast-feeding. Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant chemotherapy<br>Oxaliplatin 130mg/m2 d1 and Capecitabine 1250mg/m2 bid1-14 or other fluorouracils, every 21 or 14 days for 2 to 4 cycles, and efficacy evaluation every 2 cycles; | Drug: Oxaliplatin and capecitabine<br>* Patients receive 5-Fu and oxaliplatin based neoadjuvant chemotherapy for 3 months<br>* Other names: antiemetics;Procedure: Total Mesorectal Excision<br>* Patient receive total mesorectal excision after neoadjuvant chemotherapy<br>* Other names: TME;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response rate | the number of patients with pCR divided by the total number of patients | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 year disease-free survival | cumulative rate of survival without cancer after 3 years follow up | three years after the enrollment | 
| surgical complication rate | rate of patients who had surgical complications during the perioperative period | 30 days after the operation | 
| Toxicity of neoadjuvant chemotherapy | category and grade of adverse event during neoadjuvant chemotherapy | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal Cancer, neoadjuvant, chemotherapy