Dose-escalation Trial of Preoperative Radiotherapy and Concurrent Chemotherapy in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The aim of this study is to evaluate the increase of radiation dose administered in patients diagnosed with locally advanced rectal cancer in terms of ypRC with tolerable toxicity, using IMRT (concomitant boost technique).

Detailed Description
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The hypothesis that arises is an improvement in the proportion of pathological complete responses, resulting therapeutic gain, as a result of a higher dose of radiation delivered to the tumor volume without incurring a higher gastrointestinal toxicity to the patient or surgical complications later, thanks to the use of intensity modulated radiotherapy (concomitant boost technique) that allows us to significantly reduce the administered dose organs at risk.

Official Title
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Multicenter Dose-escalation Trial of Radiotherapy in Patients With Locally Advanced Rectal Cancer

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Radiation: 3DCRT treatment (sequential boost)
* Radiation: Dose Escalation Intensity Modulated Radiotherapy treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven diagnosis of adenocarcinoma of the rectum Clinically determined to be stage T3 or T4,N0-N2, and M0 -staged by MRI or transrectal ultrasound of the rectum Patients who are medically operable and who have resectable adenocarcinoma of the rectum at least <11cm from the anal verge Adequate liver/renal and haematological function. Eastern Cooperative Oncology Group (ECOG) performance 0-2 Age ≥ 18 years Full blood count obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3 Platelets ≥ 100,000 cells/mm3 Haemoglobin ≥ 8.0 g/dl Serum creatinine within normal institutional limits Bilirubin within normal institutional limits AST and ALT < 2.5 x the IULN Patient must sign study specific informed consent prior to study entry Exclusion Criteria: Prior systemic chemotherapy for colorectal cancer; note that prior chemotherapy for a different cancer is allowable. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Any evidence of distant metastases (M1) A synchronous primary colon carcinoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| Experimental: Treatment with IMRT Dose Escalation<br>Dose Escalation Intensity Modulated Radiotherapy treatment | Radiation: Dose Escalation Intensity Modulated Radiotherapy treatment<br>* Radiotherapy: IMRT treatment (concomitant boost technique) 25 fractions fraction 2,15Gy by administering a total dose of tumor and lymph nodes 53,75Gy on more margin. Simultaneously we will proceed to the irradiation of pelvic lymph node chains according to protocol, a division of 1,8Gy per session until a total dose of 45 Gy. Chemotherapy: According to routine clinical practice of the participating centers.<br>|
| Active Comparator: Treatment with 3DCRT<br>3DCRT treatment (sequential boost) | Radiation: 3DCRT treatment (sequential boost)<br>* Radiotherapy: 3DCRT treatment (sequential boost) 25 fractions fraction 1,8Gy by administering a total dose of 45 Gy on tumor and lymph nodes and lymph node chains more pelvic margin determined according to protocol. 3 fractions fraction 1,8Gy by sequentially administering an additional dose of tumor and lymph nodes 5,4Gy on more margin. Chemotherapy: According to routine clinical practice of the participating centers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response | Pathologic evaluation of the surgical specimen as assessed by Mandard Tumor regression scoring | Through study completion, an average of 2 years | 
| Gastrointestinal toxicity | Gastrointestinal adverse events as assessed by CTCAE v4.0 | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grade | Pathologic evaluation of the surgical specimen | Through study completion, an average of two years | 
| Disease free survival |  | Three years | 
| Overall survival |  | Five years | 
| Acute Toxicity | Acute Toxicity including anorexia, nausea, vomiting, diarrhoea, dermatitis proctitis, urinary frequency/urgency as per common toxicity criteria V4.03 | Two years | 
| Quality of Life during the treatment | Assessed by EORTC QLQC30-CR29 questionnaries | Three years after the study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMRT, Rectal Cancer, Radiation Dose Escalation