Study of Metronomic Capecitabine and Oxaliplatin Versus XELOX in Egyptian Metastatic Colorectal Cancer Patients

Study Overview
=================
Brief Summary
-----------------
Colorectal cancer (CRC) in Egypt is advanced tumors at diagnosis. Although, the dramatic increase in efficacy, reduction of mortality, and improvements in survival by the use of standard doses of chemotherapy, some CRC patients suffer from severe toxicities besides disease progression. Use of chemotherapy less than the maximum tolerated dose, with no prolonged drug free breaks incapacitates the cells to engage in progression mechanisms, suggesting that it could be a better alternative to standard dose therapy with better toxicity profile

Detailed Description
-----------------
This is a randomized phase II prospective study that included 70 (35 in each arm) metastatic Egyptian CRC cancer patients diagnosed at the National Cancer Institute, Cairo University between January 2016 and June 2018). Patients were randomly treated with either classic XELOX (arm A) or with capecitabine (2000 mg daily x 8 weeks) and oxaliplatin (30 mg/m2 weekly X 8 weeks) then 2 weeks rest (arm B). Toxicities and the survival analysis after two years for both regimens were recorded. Blood samples are taken from both groups to assess pharmacokinetics of capecitabine and its relation to dosing.

Official Title
-----------------
Clinico-pharmacological Study of Metronomic Capecitabine and Oxaliplatin Versus Classic XELOX in Egyptian Metastatic Colorectal Cancer

Conditions
-----------------
Clinical Response, Toxicity, Survival

Intervention / Treatment
-----------------
* Drug: metronomic XELOX
* Drug: Classic XELOX
* Other: Blood samples for pharmacological studies


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient age 18-70 years of both sexes. PS 0-2 and histologically proven mCRC with unresectable metastases (rectal cancer is included to left side cancers). They should have measurable lesions (that can be accurately measured in at least one dimension using calipers or ruler and measurement must be at least 20 mm using conventional techniques or 10 mm using spiral CT scan). No previous treatment for metastatic disease and had ended adjuvant treatment > 6 months. peripheral neuritis less than grade 2. Normal organ functions:(Creatinine ≤1.2, Bilirubin ≤1.2, SGOT/SGPT< 2N, HB >9gm/dl, WBC>3.5/dl with ANC >1.5/dl, Plat ≥100/dl). For patients with liver metastases, Bilirubin should not be >2.5N and transaminases not >5N. (All patients were screened for HCV and HBS Ag by PCR). Adequate cardiac functions (EF>55%) Exclusion Criteria: patients with only ascites or bone metastasis

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 70 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Classic (A)<br>patients recieving classic XELOX (oxaliplatin 130mg/m2 and capecitabine 1000mg/m2 bid) | Drug: Classic XELOX<br> <br> * Other names: Oxaliplatin;Other: Blood samples for pharmacological studies<br> <br> * Other names: No other names;|
| Experimental: metronomic (B)<br>patients recieving low dose capecitabine (2000mg daily divided in two doses for 8 weeks) and oxaliplatin (30mg/m2 weekly for eight weeks) followed by 2 weeks rest. | Drug: metronomic XELOX<br> <br> * Other names: Oxaliplatin;Other: Blood samples for pharmacological studies<br> <br> * Other names: No other names;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rates | Calculated with 95% confidence interval | two years | 
| Rate of toxicities and grades | Categorical data summarized by pecentages | two years | 
| Peak and trough levels of capecitabine and relation to dosing | Numerical data summarized by means and standard deviation | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Cox proportional hazard model | two years | 
| Overall survival | Kaplan and Meier test | Two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal cancer, metronomic capecitabine