Efficacy and Safety Study of Neoadjuvant in Treating Patients With Resectable Local Recurrent Rectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Surgical resection and adjuvant therapy has become the main treatment for resectable local recurrent rectal cancer. However the efficacy and safety of adjuvant therapy is still unknown. PURPOSE: This randomized multicenter clinical trial is studying surgical resection followed by chemo radiotherapy or neoadjuvant chemo radiotherapy followed by surgery and postoperative chemotherapy, comparing them to see the efficacy and safety, then to investigate the effect of adjuvant chemoradiotherapy for resectable local recurrent rectal cancer.

Detailed Description
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OBJECTIVES: Primary - Compare the 5-year survival rate in patients with resectable local recurrent rectal cancer treated with either surgical resection or neoadjuvant. Secondary Compare the side effect of chemo radiotherapy according to the Common Toxicity Criteria(CTC) version 2.0 in patients treated with these regimens. Compare the postoperative complications in patients treated with these regimens. Compare the recurrent rate in patients treated with these regimens. Compare the distant metastatic rate in patients treated with these regimens. OUTLINE: This is a randomized, multicenter clinical trial. Patients are stratified according to participating center, gender, age. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive surgical resection and undergo FOLFIRI for 12 cycles, from 2-4 weeks after operation. Patients undergo radiotherapy once daily 5 days a week for 5-6 weeks, from 8-12 weeks after operation. Arm II: Patients receive neoadjuvant chemoradiotherapy (mFOLFIRI for 5 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFIRI), surgery and FOLFORI for 7 cycles from 2-4 weeks after operation. After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for at least 3 years. The side effect of chemo radiotherapy, postoperative complications, recurrent rate, distant metastatic rate and 5-year survival rate will be investigated. PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study within 5 year.

Official Title
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A Randomized Multicenter Clinical Trial of Direct Surgical Resection Compared to Neoadjuvant Followed by Surgical Resection in Treating Patients With Operable Local Recurrent Carcinoma Of The Rectum

Conditions
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Rectal Cancer

Intervention / Treatment
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* Procedure: surgical resection and adjuvant therapy
* Procedure: Neoadjuvant followed by operation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Adenocarcinoma of the rectum Age:18-80 years old Received curative resection when diagnosed as rectal cancer Local recurrence happened >6 months after operation,without distant metastasis Local recurrent mass is resectable confirmed by surgeon and radiologist 6.15 days prior recruit, meet the following criteria: Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Total bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2 times ULN AST ≤ 2.5 times ULN ALT ≤ 2.5 times ULN No hepatic disease that would preclude study treatment or follow-up No uncontrolled coagulopathy Renal Creatinine clearance > 50 mL/min No renal disease that would preclude study treatment or follow-up 7.ECOG status: 0～1 Exclusion Criteria: Other rectal cancers (i.e.sarcoma,lymphoma,carcinoid,squamous cell carcinoma,or cloacogenic carcinoma) Synchronous colon cancer Hypersensitivity to fluorouracil No More than 4 weeks since prior participation in any investigational drug study Clear indication of involvement of the pelvic side walls by imaging With distant metastasis History of invasive rectal malignancy, regardless of disease-free interval Fertile patients must use effective contraception Uncontrolled hypertension Cardiovascular disease that would preclude study treatment or follow-up Lack of upper gastrointestinal tract integrity or malabsorption syndrome，active upper gastrointestinal tract bleeding Pregnant or nursing, Fertile patients do not use effective contraception Other malignancy within the past 5 years except effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum No psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgical resection and adjuvant therapy<br>Patients receive surgical resection and undergo FOLFIRI for 12 cycles, from 2-4 weeks after operation. Patients undergo radiotherapy once daily 5 days a week for 5-6 weeks, from 8-12 weeks after operation | Procedure: surgical resection and adjuvant therapy<br>* Postoperative: Drug: fluorouracil Given IV continuously, Irinotecan Given IV Radiation: radiation therapy Given 5 days a week for 5-6 weeks<br>|
| Experimental: Neoadjuvant followed by operation<br>Patients receive neoadjuvant chemoradiotherapy (mFOLFIRI for 5 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFIRI), surgery and FOLFORI for 7 cycles from 2-4 weeks after operation. | Procedure: Neoadjuvant followed by operation<br>* Preoperative: Drug: fluorouracil Given IV continuously,Irinotecan Given IV Radiation: radiation therapy Given 5 days a week for 5-6 weeks Postoperative: Drug: fluorouracil Given IV continuously,Irinotecan Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year disease free survival | Compare the 5-year survival rate in patients with resectable local recurrent rectal cancer treated with either surgical resection or neoadjuvant. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effect of chemo radiotherapy, postoperative complications, recurrent rate, distant metastatic rate,biomarkers, quality of life, toxic profile, convenience | Compare the postoperative complications in patients treated with these regimens Compare the recurrent rate in these patients Compare the distant metastatic rate in these patients Compare preoperative quality of life (QOL) of patients. Compare the toxic effects of these regimens in these patients. Compare the convenience of care in patients treated with these regimens | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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local recurrent rectal cancer, surgical resection, adjuvant therapy