Capecitabine as Radiosensitising Agent in Neoadjuvant Treatment of Locally Advanced Resectable Rectal Cancer

Study Overview
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Brief Summary
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A Phase II study aimed to evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in locally advanced resectable rectal cancer.

Detailed Description
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Preoperative chemoradiation has become a standard part of treatment protocols in stage II and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of preoperative application of chemotherapeutics and irradiation includes improved compliance, reduced toxicity and downstaging of the tumour in a substantial number of patients. The latter may enhance the rate of curative surgery, permit sphincter preservation in patients with low-sited tumours and have a positive impact on the quality of life of these patients. Orally administered capecitabine (Xeloda®, Hoffmann - La Roche Ltd, Basel, Switzerland) mimics the pharmacokinetics of continuous 5-FU infusion and makes chemoradiotherapy more patient-friendly. The mechanism of capecitabine activation, preferably in tumour cells, may further enhance its efficacy and tolerability, offering the potential for an enhanced therapeutic ratio.The aim of the present phase II study was to evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in patients with locally advanced rectal cancer. The primary endpoint of the study is a pathologically determined complete remission rate (pCR) of the disease locally and regionally. Secondly, the rate of sphincter preservation in low-sited tumours, overall downstaging rate,toxicity and survival parameters will be analysed.

Official Title
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Capecitabine as Radiosensitising Agent in Neoadjuvant Treatment of Locally Advanced Resectable Rectal Cancer

Conditions
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Resectable Rectal Cancer Clinical Stage II and III

Intervention / Treatment
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* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically verified adenocarcinoma of the rectum, resectable clinical stage II or III (IUCC TNM classification 2002); no prior radiotherapy and/or chemotherapy; World Health Organisation (WHO) performance status < 2; age at diagnosis of 18 or older; and adequate bone marrow, liver, renal and cardiac function (no history of ischemic heart disease). Exclusion Criteria: A history of prior malignancy other than non-melanoma skin cancer or in situ carcinoma of the cervix

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Capecitabine|Chemotherapy with capecitabine of 1650 mg/m2 daily dose will be administered orally, divided into two equal doses given 12 hours apart, during radiotherapy(45 Gy 1,8 Gy/fr), including weekends|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete pathological remission rate | after pathological examination of resected specimen | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of sphincter preservation in low-sited tumours | after the operation | 9 weeks | 
| toxicity of combined modality treatment (Number of Participants with Adverse Events) | During preoperative treatment, patients will be evaluated weekly for acute toxicity and compliance with the protocol. Clinical examination and complete blood count will be performed and body weight was measured. Toxic side effects will be assessed according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) (version 2.0). Patients will be followed every three month for the first two years after the last cycle of adjuvant chemotherapy and thereafter every six month up to 5th year. | 5 weeks | 
| overall downstaging rate | after the pathological examination of resected specimen | 9 weeks | 
| overall survival | Overall survival is defined as the time from inclusion to the date of death from any cause or to the date of last follow-up. | 5 years | 
| local control | Local control is defined as the time from inclusion to the date of local recurrence | 5 years | 
| relapse-free survival | Relapse-free survival iss defined as the time from inclusion to the first occurrence of disease relapse (local or distant), death or date of last follow-up. | 5 years | 
| long-term rectal and urogenital morbidity |  | 2 years after the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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capecitabine, chemoradiation, rectal cancer, phase II study