A Trial of High Intensity Versus Low Intensity Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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Neoadjuvant chemoradiotherapy (CRT) has been the standard therapy for local advanced rectal cancer. Pathological complete response (pCR) is an important prognostic factor for local control and survival. A high intensity CRT increases not only the pCR rate, but also toxicity, especially diarrhea. Compared with traditional RT technique, intensity-modified radiation therapy (IMRT) can decrease the toxicity of diarrhea because of low volume of high dose for small bowel. Therefore, IMRT technique provides an opportunity to improve the dose intensity of neoadjuvant CRT. The investigators hypothesize that a higher treatment dose induces a high rate of pCR and design a two-arm trial. in this trial, low intensity CRT includes the whole pelvic irradiation of 50Gy together with Oxaliplatin and Capecitabine weekly. While in high intensity group, additional concomitant 5Gy for primary tumor and a cycle of Xelox are prescribed. All patients will receive a total mesorectal excision (TME) 8 weeks after CRT.

Official Title
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An Open Label, Randomized, Multi-center, Phase II/III Trial of High Intensity Versus Low Intensity Neoadjuvant Chemoradiotherapy With Intensity-modified Radiation Therapy (IMRT) in Local Advanced Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Capecitabine
* Radiation: Radiotherapy
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with rectal adenocarcinoma Clinical staged T3/4 or any node-positive disease Age: 18-75 years Karnofsky Performance Status > 80 Adequate bone marrow reserve, renal and hepatic functions Without previous antitumoural chemotherapy No evidence of metastatic disease Written informed consent before randomization Exclusion Criteria: Previous pelvis radiotherapy. Previous antitumoural chemotherapy Clinically significant internal disease

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High intensity group<br>(RT 55Gy + CapOx) + a cycle of Xelox + Surgery | Drug: Oxaliplatin<br>* CRT:50mg/m2,IV,weekly*5 cycle CT: 130mg/m2,IV,d1,q 21 day<br>Drug: Capecitabine<br>* CRT:625mg/m2,bid,d1-5,q week RT:1000mg/m2,bid,d1-14,q 3 weeks<br>Radiation: Radiotherapy<br>* High intensity group:55Gy Low intensity group:50Gy<br>Procedure: Surgery<br>* Lower anterior resection or abdominoperineal resection<br>|
| Active Comparator: Low instensity group<br>(RT 50Gy + CapOx) + Surgery | Drug: Oxaliplatin<br>* CRT:50mg/m2,IV,weekly*5 cycle CT: 130mg/m2,IV,d1,q 21 day<br>Drug: Capecitabine<br>* CRT:625mg/m2,bid,d1-5,q week RT:1000mg/m2,bid,d1-14,q 3 weeks<br>Radiation: Radiotherapy<br>* High intensity group:55Gy Low intensity group:50Gy<br>Procedure: Surgery<br>* Lower anterior resection or abdominoperineal resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of pathological complete response (pCR) |  | within 14days after surgery | 
| toxicity |  | every week during radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local recurrence |  | every half year after surgery | 
| disease-free survival |  | every half year after surgery | 
| overall survival |  | every half year after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant chemotherapy, locally advanced rectal cancer, intensity-modulated radiation therapy, pathological complete response