Preoperative Chemo-radiation With IG-IMRT Dose Escalation for Locally Advanced Rectal Cancers

Study Overview
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Brief Summary
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Hypothesis : Therapeutic intensification by increasing the dose delivered to the tumor by RCMI (conformational radiotherapy by intensity modulation) in order to reduce local relapse, often associated with poor prognosis Primary objective: evaluate the rate of tumor sterilization and the toxicities of RTCT with concomitant boost in intensity modulation in patients with rectal cancer CT3-T4 and / or cN1-2.

Official Title
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Preoperative Chemo-radiation With IG-IMRT Dose Escalation for Locally Advanced Rectal Cancers: Phase 2 Study (RADICAL)

Conditions
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Advanced Rectal Cancers

Intervention / Treatment
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* Radiation: Preoperative chemo-radiation with IG-IMRT dose escalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the rectum cT3 or cT4 or cN+, M0 and for which CPR recommends preoperative radiochemotherapy Tumor <15 cm of the anal margin in rigid or subperitoneal rectoscopy at the MRI Tumor potentially resectable from the outset, or considered to be resectable after radiochemotherapy Operable Patient Age between 18 and 75 OMS performance status 0-2 No co-morbidity likely to prevent the delivery of treatment Adequate contraception for men, and for non-menopausal women Neurotrophic neutrophils 1500 / mm3, platelets 100 000 / mm3, and hemoglobin 10 g / dL Bilirubin ≤ 1.5 times the upper limit of normal (LNS), ASAT and ALAT ≤ 1.5LNS, Alkaline phosphatase ≤ 1.5 LNS Creatinine clearance> 50 mL / min Patient must have been informed and must have signed the specific informed consent form. Patient must be affiliated to a Social Health Insurance. Exclusion Criteria: Remote metastasis Cancer not resectable Contraindication to capecitabine and its excipients Previous history of pelvic radiotherapy or previous chemotherapy History of inflammatory bowel or rectum disease History of angina pectoris monitored or myocardial infarction or heart failure Active active infection or other serious underlying condition that may prevent the patient from receiving treatment Other concomitant cancer, or history of cancer other than in situ cancer of the treated cervix or basal cell carcinoma or squamous cell carcinoma Patient already included in another therapeutic trial with an experimental molecule Pregnant woman, likely to be pregnant or nursing Persons deprived of their liberty or under guardianship Patient unable to comply with the required medical follow-up for geographic, social or psychological reasons

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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Accepts Healthy Volunteers

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: Treatment<br>- Treatment : concomitant preoperative radio-chemotherapy (during 5 weeks) Chimiotherapy: Capecitabine 1600 mg/m2/j ; 5/7 days during the 5 weeks of radiotherapy Radiotherapy RT + SIB-IMRT (5 weeks ; 5 sessions/week ; 25 sessions): Pelvic prophylactic dose of 45 Gy (1,8 Gy/session); boost with a dose of 60 Gy on the tumor PTV (2,4 Gy/session) - Total dose: 60 Gy in 25 sessions during 5 weeks. - TME surgery (8 weeks after the end of treatment) | Radiation: Preoperative chemo-radiation with IG-IMRT dose escalation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete histological response rate | Absence of residual cancer cells on the final analysis of the tumor and lymph node | at 8 weeks after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance | Toxicity is assessed according to the NCI-CTCAE toxicity scale version 4.0 | at 1, 2, 3, 4, 5 and 13 weeks after inclusion and at 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dose escalation, chemo-radiation, rectum cancer, phase 2