Prospective Study of Short Course Radiation Therapy Followed by Neoadjuvant Chemotherapy and Surgery in Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate total neoadjuvant therapy (TNT) using short course radiation therapy (SCRT) followed by full course of chemotherapy then surgery in locally advanced rectal cancer. The main questions it aims to answer are: Is total neoadjuvant treatment in this design safe & tolerable? Impact of this design on treatment related outcomes in terms of pathological and clinical responses.

Detailed Description
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Patients will be assigned to an experimental arm in which preoperative short course 5 x 5 Gy radiation therapy is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin) and surgery within 4-6 weeks

Official Title
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Prospective Phase II Study of Hypofractionated Short Course Radiation Therapy Followed by Neoadjuvant Chemotherapy and Surgery in Locally Advanced Rectal Cancer

Conditions
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Locally Advanced Rectal Carcinoma

Intervention / Treatment
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* Radiation: short course radiation therapy followed by 6 cycles of CAPOX then surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological proof of rectal adenocarcinoma. Tumors located within 15 cm and not less than 4 cm from anal verge. Age: ≥ 18 years. Locally advanced resectable rectal cancer (cT3/4 N0- Any T N+ve). ECOG Performance Status: 0-2. Exclusion Criteria: Non-epithelial rectal malignancy such as sarcoma or lymphoma. Unresectable tumors in which surgery will never be possible even if substantial tumor downsizing is seen. Recurrent rectal cancer. Previous history of malignancy within the last 5 years. Previous pelvic irradiation. Psychiatric or addictive disorder that would preclude study therapy. Concurrent uncontrolled medical conditions. Pregnancy or breast feeding. Any contraindication to surgery. Extensive peripheral neuropathy.

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: Short course RT followed by full course of chemotherapy then surgery<br>Short course radiation therapy ( 25 Gy/ 5 fractions/ 1 week) , followed by 6 cycles of chemotherapy CAPOX, followed 4-6 weeks by surgery. | Radiation: short course radiation therapy followed by 6 cycles of CAPOX then surgery<br>* Short course RT 5 x5 Gy followed by 6 cycles CAPOX then surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete response (pCR) | No residual disease in surgical specimen | within 30 days | 
| clinical complete response(cCR) | No residual disease after end of radiation and chemotherapy by examination,imaging and colonoscopy | within 30 days | 
| Sphincter saving surgery | Patients who were deemed abdomino-perineal resection before treatment start & were able to undergo low anterior resection after end of treatment | within 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control | defined as the period calculated from the date of end of treatment to the date of occurrence of loco-regional failure. | 3 years | 
| Overall survival | defined as period from diagnosis till last follow up or death from any cause | 3 years | 
| Disease free survival | defined as the period calculated from the date of end of treatment to the date of occurrence of loco-regional failure or distant failure, whichever comes first. | within 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced rectal cancer- short course radiation - chemotherapy-surgery