Clinical Effect of Neoadjuvant Hierarchical Treatment Based on Chemotherapy

Study Overview
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Brief Summary
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Clinical effect of neoadjuvant hierarchical treatment based on chemotherapy for T3-4N0-2M0 middle and lower rectal cancer

Detailed Description
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By setting 3-Year disease-free survival (DFS) as main objective, the treatment strategy will be optimizing as neoadjuvant chemotherapy alone and chemo-radio-chemo sequential treatment.

Official Title
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Clinical Effect of Neoadjuvant Hierarchical Treatment Based on Chemotherapy for T3-4N0-2M0 Middle and Lower Rectal Cancer

Conditions
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Rectum Cancer

Intervention / Treatment
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* Procedure: TME
* Radiation: Concurrent chemo-radiotherapy
* Drug: neoadjuvant CT
* Drug: adjuvant CT


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Pathologically confirmed to be rectal adenocarcinoma. Distance < 10cm from the end of the tumor to the anal verge found on colonoscopy Tumor in stage T3-4N0-2 (pelvic MRI evaluation) Patients without distant metastases (such as liver and peritoneum, lungs, aortic lymph nodes) Patients with Karnofsky score greater ≥ 70 WBC > 3.5 x 109/ml , PLT > 10 x 109/ml , TBIL<22.2 umol/l , BUN <7.14mmol/l , Cr<132umol/l or Ccr > 50ml/min (Evaluated using the Cockcroft-Gault formula: Creatinine clearance (male) = {(140 - age) x LBM (kg)} / {plasma creatinine (mg/dl) x 72} ; Creatinine clearance (female) = 0.85 x {(140 - age) x LBM(kg)}/ { plasma creatinine (mg/dl) x 72}) Patients must sign the informed consent form Female subjects must be contraceptive during the trial Patients who did not receive any form of chemotherapy and radiotherapy No other important related diseases (such as other tumors, severe heart disease and central nervous system diseases, etc.) Age must be equal or more than 20 and must be equal or less than 70 Exclusion criteria Previously received radiation therapy, chemotherapy or anti-tumor biological therapy Previously received immuno-suppressive therapy Participation in interventional clinical trial over the past time Suffering from malignant colonic neoplasms simultaneously With peripheral neuropathy(above WHO I level) Affected cognitive abilities because of neurological or psychiatric abnormalities Including central nervous system metastasis Medical history of severe allergies or allergic constitution Severe pulmonary or heart disease history Female patients who are in pregnancy or lactation and refuse contraception Previously with other malignant tumors Exit criteria Occurrence of bleeding, obstruction, perforation and other complications Occurrence of distant metastasis during the period of neoadjuvant therapy Adverse reactions, not be tolerated and do not want to continue to receive treatment Patients voluntarily quit Capecitabine-related Grade 4 Hand-Foot Syndrome

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This strategy is called neoadjuvant hierarchical treatment based on chemotherapy for rectal cancer. All patients with T3-4N0-2M0 middle and lower rectal caner will firstly receive neoadjuvant chemotherapy consisting of four cycles of XELOX. After four cycles, the patients achieved cCR or cPR will be perform the operation. And the patients who can not achieve cCR or cPR after the four cycles, then concurrent chemoradiotherapy will be added.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperative neoadjuvant CT<br>Give neoadjuvant chemotherapy for four cycle ,if achieve cCR or cPR after four cycles neoadjuvant chemotherapy , receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy | Procedure: TME<br>* Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus. At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.<br>Drug: neoadjuvant CT<br>* CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks<br>* Other names: neoadjuvant chemotherapy;Drug: adjuvant CT<br>* CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks<br>* Other names: adjuvant chemotherapy;|
| Experimental: Preoperative neoadjuvant CT-RCT<br>Give neoadjuvant chemotherapy for four cycle ,if not achieve cCR or cPR after four cycle neoadjuvant chemotherapy ,give concurrent chemo-radiotherapy,then additional neoadjuvant chemotherapy for 2 cycles ,then receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy | Procedure: TME<br>* Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus. At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.<br>Radiation: Concurrent chemo-radiotherapy<br>* Three-dimensional conformal radiotherapy as following: CTV 44Gy/22 times＋GTV1 6Gy/3 times(2Gy/time/day，5 days a week，totally 5 weeks),if rectal tumors do not regress obviously, additional GTV2 is necessary, 5.4Gy/3 times (1.8Gy/time/day). At the same time, Capecitabine (850mg/m2, two times every day) will be taken on radiotherapy day<br>* Other names: neoadjuvant RCT;Drug: neoadjuvant CT<br>* CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks<br>* Other names: neoadjuvant chemotherapy;Drug: adjuvant CT<br>* CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks<br>* Other names: adjuvant chemotherapy;|
| Active Comparator: Concurrent chemo-radiotherapy<br>Give concurrent chemo-radiotherapy ,then receive Total Mesorectal Excision(TME) ,then received the complete adjuvant therapy | Procedure: TME<br>* Find the hypogastric nerve trunk in front of sacral promontory and protect it,be careful to use electrocautery hemostasis biased toward the side of rectal when handle lateral ligament of rectum and middle rectal artery and avoid to damage the pelvic plexus. At least a 2-cm margin to the lower edge of the tumor is adequate for distal bowel resection. Resect 5cm length distal rectal or all of the mesorectum.Check the integrity of the mesorectum in postoperative routine examination. Double stapling method is used for all low anastomosis operations.<br>Radiation: Concurrent chemo-radiotherapy<br>* Three-dimensional conformal radiotherapy as following: CTV 44Gy/22 times＋GTV1 6Gy/3 times(2Gy/time/day，5 days a week，totally 5 weeks),if rectal tumors do not regress obviously, additional GTV2 is necessary, 5.4Gy/3 times (1.8Gy/time/day). At the same time, Capecitabine (850mg/m2, two times every day) will be taken on radiotherapy day<br>* Other names: neoadjuvant RCT;Drug: adjuvant CT<br>* CAPEOX protocol:Oxaliplatin 130mg/m2 ivgtt 2-6h dl;(Capecitabine 1000mg/m2 2 times a day lasts for 14 days Repeat every 3 weeks<br>* Other names: adjuvant chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) | the treatment strategy will be optimizing as neoadjuvant chemotherapy alone and chemo-radio-chemo sequential treatment. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgery related mortality and complication | Surgery related mortality and complication | 3 years | 
| Resection rate of R0 | Resection rate of R0 | 3 years | 
| Pathologic complete remission (pCR) rate | Pathologic complete remission (pCR) rate | 3 years | 
| Tolerance after neoadjuvant treatment | Tolerance after neoadjuvant treatment | 3 years | 
| Predictor efficacy of neoadjuvant chemotherapy for DFS | Predictor efficacy of neoadjuvant chemotherapy for DFS | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant Chemotherapy