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

Phase 2
Completed
Conditions
Clinical Response
Toxicity
Survival
Interventions
Drug: Classic XELOX
Drug: metronomic XELOX
Other: Blood samples for pharmacological studies
Registration Number
NCT04425564
Lead Sponsor
National Cancer Institute, Egypt
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
metronomic (B)Blood samples for pharmacological studiespatients 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.
Classic (A)Blood samples for pharmacological studiespatients recieving classic XELOX (oxaliplatin 130mg/m2 and capecitabine 1000mg/m2 bid)
Classic (A)Classic XELOXpatients recieving classic XELOX (oxaliplatin 130mg/m2 and capecitabine 1000mg/m2 bid)
metronomic (B)metronomic XELOXpatients 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.
Primary Outcome Measures
NameTimeMethod
Peak and trough levels of capecitabine and relation to dosingTwo years

Numerical data summarized by means and standard deviation

Rate of toxicities and gradestwo years

Categorical data summarized by pecentages

response ratestwo years

Calculated with 95% confidence interval

Secondary Outcome Measures
NameTimeMethod
Overall survivalTwo years

Kaplan and Meier test

Progression free survivaltwo years

Cox proportional hazard model

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