Safety Study of Capecitabine With Radiation in Elderly Rectal Cancer

Study Overview
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Brief Summary
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This phase I study is designed to determine the maximum tolerant dose of capecitabine when used in preoperative concurrent chemo-radiation for locally advanced rectal patients over 75 years old.

Detailed Description
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It is proved that preoperative concurrent chemo-radiotherapy can improve both local control and overall survival in stage II/III rectal cancer patients. But elderly patients, especially patients over 75 years were hardly involved in related clinical trials considered of their fragility. Several retrospective study showed that old rectal cancer patients would also benefit from concurrent chemo-radiation, with acceptable toxicity. Several new drug, such as capecitabine, also seem to be safety for elderly cancer patients. But few prospective study has been carried out. The investigators designed this phase I study, to explore the maximum tolerant dose of capecitabine in preoperative concurrent chemoradiation for elderly stage II/III rectal cancer patients, as well as to evaluate safety.

Official Title
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Phase I Study of Preoperative Concurrent Chemo-radiation With Capecitabine in Elderly Rectal Cancer Patients

Conditions
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Rectal Neoplasms

Intervention / Treatment
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* Drug: capecitabine
* Drug: Capecitabine
* Drug: Capecitabine
* Drug: Capecitabine
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th). KPS status no less than 70; Charlson comorbidity no more than 3. life expectancy more than 6 months. hemoglobin >= 100g/L, white blood cell >= 3.5*10E9/L, neutrophil >= 1.5*10E9/L, platelet >= 100*10E9/L.Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal. do not have allergy history to thymidine phosphorylase. do not receive surgery ( except palliative colostomy) or chemotherapy or other anti-cancer treatment no previously pelvic irradiation history informed consent signed Exclusion Criteria: other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma previous pelvic irradiation history receiving surgery (except palliative colostomy), chemotherapy or other anti-cancer treatment allergy history to thymidine phosphorylase active infection existed severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day≥11.1mmol/L）, severe cardiac arrhythmia， etc. anticipate other clinical trials in four weeks before enrollment

Ages Eligible for Study
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Minimum Age: 75 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1000mg<br>capecitabine 1000mg/m2/d d1-14, d22-25 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: capecitabine<br>* oral pills, 1000mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation<br>* Other names: stare 1;|
| Experimental: 1200mg<br>capecitabine 1200mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: Capecitabine<br>* oral pills, 1200mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation<br>* Other names: stare 2;|
| Experimental: 1350mg<br>capecitabine 1300mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: Capecitabine<br>* oral pills, 1350mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation<br>* Other names: stare 3;|
| Experimental: 1500mg<br>capecitabine 1500mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: Capecitabine<br>* oral pills, 1500mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation<br>* Other names: stare 4;|
| Experimental: 1650mg<br>capecitabine 1650mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: Capecitabine<br>* oral pills, 1650mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation<br>* Other names: stare 5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experienced Dose Limited Toxicity | Dose related toxicity is defined as follows:1. luecopenia > grade 2; granular cell decrease > grade 2; anemia > grade 1; platelet > grade 1;SGPT/SGOT elevation > grade 1; ALP > grade 1; GGT > grade 1; Tbil > grade 1;renal function damag > grade 2;Non-gradular cell decreased fever > grade 1;nausea/vomiting > grade 1; fatigue > grade 2; weight loss > grade 2;gastritis > grade 2; dairrea > grade 2; abdominal pain > grade 2; upper gastrointestinal bleeding > grade 1;other toxic reaction > grade 2;KPS < 50 during the treatment | up to 7 weeks from start of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aged, rectal neoplasms, chemoradiotherapy, clinical trials, phase I, capecitabine