Adjuvant Chemotherapy in Patients With Clinical Stage III Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of adjuvant chemotherapy in patients with clinical stage III rectal cancer who received neoadjuvant chemoradiotherapy on the basis of postoperative pathological stage.

Detailed Description
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Previous studies have proved that neoadjuvant radiotherapy can decrease the rate of local recurrence rather than distal metastases in advanced rectal cancer. Moreover, the local control was not responsible for survival benefit. Adjuvant chemotherapy is capable of eliminating the micrometastasis, rendering better prognosis to rectal cancer. However, the application of adjuvant chemotherapy depends largely on the evidence from colon cancer. At present, controversy remains on the clinical value of adjuvant chemotherapy in patients with rectal cancer who received neoadjuvant chemoradiotherapy. Besides that, the pathological stage followed by neoadjuvant chemoradiotherapy may have an effect on the evaluation of adjuvant chemotherapy. According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil. For patients with yp stage II or III, the study aims to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone.

Official Title
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Efficacy of Adjuvant Chemotherapy in Patients With Clinical Stage III Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Pathology-oriented, Prospective, Multicenter, Randomized, Open-label, Parallel Group Clinical Trial

Conditions
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Rectal Neoplasms

Intervention / Treatment
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* Drug: Capecitabine
* Drug: mFOLFOX6 or CAPOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The lesion must be within 12 cm of the anus as measured by endoscopy Histologically confirmed diagnosis of rectal carcinoma CT, MRI and EUS verified as clinical stage III rectal cancer without involvement of other organs Without multiple primary cancer Sufficient organ function Able to provide written informed consent Exclusion Criteria: Younger than 18 years or older than 75 years Synchronous or metachronous malignancy within 5 years. Patients with Intestinal obstruction or perforation or bleeding who require emergency surgery. Patients with a history of pelvic irradiation. ASA grade IV or V. Women who are pregnant (confirmed by serum b-HCG in women of reproductive age) or breast feeding. Severe mental illness. Patients with severe emphysema, interstitial pneumonia, or ischemic heart disease who can not tolerate surgery. Patients who received steroid therapy within one month. Patients or family members misunderstand the conditions and goals of this study.

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 |
| --- | --- |
| No Intervention: Observation<br>Observation for patients with pathological complete response or yp stage I(According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil) | |
| Experimental: 5-fluorouracil<br>Capecitabine for patients with pathological complete response or yp stage I Capecitabine 1250 mg/m2 twice daily for 14 days in a 3-week cycle to be administered orally after food, three cycles(According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil ) | Drug: Capecitabine<br>* According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil. For patients with yp stage II or III, the study aims to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone.<br>* Other names: Xeloda;|
| Experimental: 5-fluorouracil alone<br>5-fluorouracil alone for patients with yp stage II or III Capecitabine 1250 mg/m2 twice daily for 14 days in a 3-week cycle to be administered orally after food, three cycles(According to the postoperative pathological stage, the present study was designed as a superiority trail for patients with yp stage II or III to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone) | Drug: Capecitabine<br>* According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil. For patients with yp stage II or III, the study aims to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone.<br>* Other names: Xeloda;|
| Experimental: mFOLFOX6 or CAPOX<br>Oxaliplatin combined with 5-fluorouracil for patients with yp stage II or III mFOLFOX6 (leucovorin 400 mg/m2 as a 2-hour infusion, and the concurrent administration of oxaliplatin 85 mg/m2 as a 2-hour infusion, followed by a bolus of 5-FU 400 mg/m2 within 15 min and 46-hour infusion of 5-FU 2400 mg/m2 on day 1 every 2 weeks), three cycles or CAPOX (oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, followed by capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks), three cycles( According to the postoperative pathological stage, the present study was designed as a superiority trail for patients with yp stage II or III to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone) | Drug: mFOLFOX6 or CAPOX<br>* According to the postoperative pathological stage, the present study was designed as a non-inferiority trail for patients with pathological complete response or yp stage I to compare the long-term outcomes of observational group and those receiving 5-fluorouracil. For patients with yp stage II or III, the study aims to compare the effect of oxaliplatin combined with 5-fluorouracil and 5-fluorouracil alone.<br>* Other names: 5-Fu-leucovorin-oxaliplatin or xeloda-oxaliplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Calculated from the date of surgery to the date of recurrence | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Calculated from the date of diagnosis to the date of death from any cause | 3-year, 5-year | 
| Disease free survival | Calculated from the date of surgery to the date of recurrence | 5-year | 
| The rate of local recurrence | The ratio of the number of local recurrence to the total patients | 3-year | 
| The rate of adverse events resulted from chemotherapy | The ratio of the number of patients experienced adverse events to the total patients | 3-year | 
| The quality of life postoperatively | The European Organization for Research and Treatment (EORTC)-QLQ-C30 HRQL questionnaire was assessed with repeated measures at regular intervals postoperatively at months 3, 6, 9, 12, 18, and 24 | 3-month, 6-month, 9-month, 12-month, 18-month, 24-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal Neoplasms, Adjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy