Induction Chemotherapy Followed by Short Course Radiotherapy in Rectal Cancer

Study Overview
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Brief Summary
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A Single-arm phase II trial evaluating induction chemotherapy with FOLFIRINOXm followed by short course radiotherapy (RT) in locally advanced rectal carcinoma

Detailed Description
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Total neoadjuvant treatment (TNT) is currently the standard of care in the management of locally advanced rectal cancer since recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven. Two strategies of TNT are validated so far : induction chemotherapy with FOLFIRINOX followed by long course radio-chemotherapy (RCT) or short course RT (5x5 Gy) followed by consolidation chemotherapy with CAPOX (capecitabine and oxaliplatin) or FOLFOX (5 FU and oxaliplatin) . The objective of investigators is to evaluate pathological complete response with a new strategy of TNT consisting in induction chemotherapy with FOLFIRINOXm followed by short course RT and a delayed surgery.

Official Title
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Induction Chemotherapy With FOLFIRINOX ( 5 Fluorouracil, Oxaliplatine and Irinotecan) Followed by Short Course Radiotherapy in Locally Advanced Rectal Cancer

Conditions
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Rectal Cancer, Locally Advanced

Intervention / Treatment
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* Drug: Chemotherapy With FOLFIRINOX ( 5 Fluorouracil, Oxaliplatine and Irinotecan)
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: World Health Organization (WHO) performance status : 0 or 1 Histologically proven rectal adenocarcinoma < 10 cm from anal margin on rectoscopy clinically T3 (cT3) or clinically T4 (cT4) and/ or N+ non metastatic rectal cancer Neutrophil count > 1500 e/mm3 Platelet count >100000 Hemoglobin > 10 g/dl ( transfusion allowed) Normal bilirubin level Creatinine clearance > 50 ml/mn Exclusion Criteria: Distant metastases History of chemotherapy or radiotherapy Grade 1 neuropathy Patient undergoing treatment for another cancer Active infection or severe comorbidities contraindicating chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Induction CT followed by short course RT<br>Induction chemotherapy with modified 5 fluorouracil, oxaliplatin and irinotecan followed by short course radiotherapy ( 5x5 Gy), then 5 fluorouracil and oxaliplatin based chemotherapy. Surgery will be performed 6 to 8 weeks after completion of RT. | Drug: Chemotherapy With FOLFIRINOX ( 5 Fluorouracil, Oxaliplatine and Irinotecan)<br>* Induction chemotherapy with six cycles of modified 5 fluorouracil,oxaliplatin and irinotecan followed by short course radiotherapy (RT) (5x5 Gy), then two cycles of 5 fluorouracil and oxaliplatin based chemotherapy and surgery will be performed 6 to 8 weeks after completion of RT. After surgery , continuation of chemotherapy with 4 cycles of 5 fluorouracil and oxaliplatin regardless of pathological response<br>Radiation: Radiotherapy<br>* Short Course Radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response | no tumor identified in the rectum or associated lymph nodes by final pathology following surgical resection | 1 month after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | first relapse after surgery | 3 years | 
| overall survival | death | 3 years | 
| objective response rate to induction chemotherapy |  | immediately after completion of 6 cycles of chemotherapy ( each cycle is 14 days) |