Study of Postoperative Concurrent Chemo-radiation With Capecitabine in Elderly Rectal Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to seek the proper dose of capecitabine in post-operative concurrent chemotherapy for stage II/III elderly rectal cancer patients receiving radical surgery, and evaluate the toleration of this modality in such patients.

Detailed Description
-----------------
For those younger locally advanced (stage II/III) rectal cancer patients (usually means patients less than 70), it is suggested that after radical surgery, patients should receive concurrent chemo-radiation. Capecitabine is a widely used chemotherapy medicine under such condition. Based on experience, the investigators think this modality can also be tolerated by patients over 70, and will increase local control rate as which has been proved in younger ones. As the first step to test this hypothesis, we designed this phase I study to seek the proper dose of capecitabine, a widely used oral chemotherapy medicine, in postoperative concurrent chemo-radiation for stage II/III rectal cancer patients over 70, and to evaluate the safety of this modality in this group of patients.

Official Title
-----------------
Phase 1 Study of Postoperative Capecitabine With Concurrent Radiation in Elderly With Stage II/III Rectal Cancer

Conditions
-----------------
Rectal Neoplasms

Intervention / Treatment
-----------------
* Drug: Capecitabine
* Drug: Capecitabine
* Drug: Capecitabine
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: rectal adenocarcinoma, pathological stage II/III(T3-4 or N+, UICC 2002), radical surgery received. interval between surgery and enrollment no less than two week and no more than 3 months. KPS status no less than 70; life expectancy no less than 6 months. without life-threatening complications, such as severe hypertension, coronary heart disease, cerebral vascular disease, uncontrolled diabetes, etc. without severe drug allergy history. hemoglobin >= 100g/L, white blood cell >= 3.5*10E9/L, neutrophil >= 1.5*10E9/L, platelet >= 100*10E9/L. Creatin <= 1.5* ULN(upper limit of normal), Total bilirubin <= 2.5 ULN, AST and AST <= 2.5* ULN, AKP <= 2.5*ULN do not receive chemotherapy before six months from enrollment. no previously pelvic irradiation history informed consent signed Exclusion Criteria: other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma allergy history to thymidine phosphorylase previous pelvic irradiation history receiving adjuvant chemotherapy in six months before enrollment 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. life expectancy less than 6 months estimated cannot finish treatment attend other clinical trials in four weeks before enrollment receive other anti-cancer treatment currently other conditions which regarded illegal by censors with full reasons. for example, some conditions may conflict from the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 71 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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, d22-35 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: stair 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: stair 2;|
| Experimental: 1400mg<br>capecitabine 1400mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients. | Drug: Capecitabine<br>* oral pills, 1400mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation.<br>* Other names: stair 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: stair 4;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Related Toxicity | dose related toxicity is defined as follows:1. WBC damage >= grade 3; granular cell decrease >= grade 3; hemoglobin >= grade 2; platelet >= grade 2;SGPT/SGOT elevation >= grade 2; ALP >= grade 2; GGT >= grade 2; Tbil >= grade 2;renal function damage: BUN/Cr elevation >= grade 2;Non-gradular cell decreased fever >= grade 2;nausea/vomiting >= grade 2; fatigue >= grade 3; weight loss >= grade 3;gastritis >= grade 3; dairrea >= grade 3; abdominal pain >= grade 3; pancreatitis >= grade 2; upper gastrointestinal bleeding >= grade 2;other toxic reaction >= grade 3;KPS < 50 during the treatment | up to 9 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rectal neoplasms, aged, radiotherapy, drug therapy, dose-escalation, capecitabine