Neo-adjuvant Short Course Chemo-radiation Therapy in Locally Advanced Rectal Cancer Patients

Study Overview
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Brief Summary
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The primary objective of this trial is to assess the safety and feasibility of 5-FU when given concurrently with5 Gy x 5 fractions IMRT. The secondary endpoint is to assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.

Detailed Description
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Neo-adjuvant radiotherapy is associated with the improvement of local control for rectal cancer. For locally advanced stage II-III resectable rectal cancer, either preoperative short-course radiotherapy of 25 Gy in 5 consecutive days or long-course chemo-radiotherapy followed by radical Total Meso-rectal Excision is recommended. The Swedish Rectal Cancer Trial has demonstrated the lower rate of early toxicity of short course radiotherapy when compared to chemo-radiation. Short-course irradiation reduced the risk of local recurrence with evidence of overall survival improvement. Short-course regimen is less expensive and more convenient, especially in centers with long waiting lists. Two meta-analyses showed that short course is as effective as long course chemo-radiation in the management of locally advanced rectal cancer in the terms of sphincter preservation rates, down-staging, R0 resection, local control, and grade 3-4 toxicity. Despite reduction in local-regional recurrence risk with neo-adjuvant short course radiotherapy, distant disease recurrence remains a substantial risk for patients with locally advanced disease. In a controlled randomized trial, a short course radiotherapy followed by consolidation chemotherapy prior to surgery yielded superior overall survival outcomes compared to chemo-radiotherapy, without significant differences in disease-free survival, nor local or distant disease control rates. The phase III RAPIDO and STELLAR clinical trials are also evaluating short course radiotherapy and consolidation chemotherapy. The Stockholm III trial was a 3-arm trial that compared short-course RT with the standard 1-week delay to surgery, short-course RT with a 4- to 6-week delay to surgery, and long-course chemoradiation with a 4- to 6-week delay to surgery. The results show similar outcomes between the groups, but delaying the surgery after short-course RT decreased the rates of high-grade toxicity and allowed for an expedited treatment program.

Official Title
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Evaluation of the Efficacy and Toxicity of Neo-adjuvant Short Course Radiation Therapy Concurrently With Continuous Infusion 5-fluorouracil in the Management of Locally Advanced Rectal Cancer Patients

Conditions
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Neo-adjuvant Short Course Chemo-radiotherapy in Locally Advanced Cancer Rectum

Intervention / Treatment
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* Drug: short course chemo-radiation with 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological confirmed cancer rectum Age between 20-80 Clinical T3\4 or node positive disease by MRI Exclusion Criteria: Early stage cancer rectum M1 disease confirmed by imaging or pathological

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Other: neoadjuvant chemo-radiation<br>Short-course RT: 5 fractions of 5 Gy to a total dose of 25 Gy over 5 consecutive days. IMRT plans are generated with 6 MV photons. Dose-escalated concurrent 5-FU: The 3 doses levels of 5-FU are 100, 150, and 200 mg/m2/d. 5-FU will be given by continuous infusion for 20 hours every day starting on the morning of radiation. mFOLFOX: will be given 2 weeks after concurrent chemoradiation for a total of 4 cycles, with each cycle being 14 days. Surgery will be omitted in patients with complete pathological response and proceed to adjuvant chemotherapy. If patient develops progressive or metastatic disease, he/she will be omitted from the investigators study. The surgery will be considered 4-8 weeks after end of therapy. Adjuvant mFOLFOX6: 6 cycles chemotherapy will begin between 4 weeks and 8 weeks after surgery. Toxicities assessment: be using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | Drug: short course chemo-radiation with 5-fluorouracil<br>* neo-adjuvant short course chemo-radiation in locally advanced rectal cancer patients followed by delayed surgery<br>* Other names: 5-fu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment adverse events as assessed by National Cancer Institute Common Terminology Criteria for adverse events version 4.0 | Dose limiting toxicity is defined as any of the following occurring during chemo radiation or within 21 days from the completion of the treatment like grade 4 non hematological toxicity, grade 4 febrile neutropenia, grade 4 thrombocytopenia or neutropenia toxicity lasting 7 days, grade 3 non hematological toxicity preventing treatment more than 3 days, elevation of ALT or AST more than 10 the upper limit of normal for 7 days | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery. | assess disease local control measured by disease free survival in months and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery measured by either complete pathological response 0r partial response or no response | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CCRTH