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

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

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

Study Overview

• Status: Completed
• Conditions: Toxicity; Survival; Clinical Response
• Intervention / Treatment: Drug: Classic XELOX; Other: Blood samples for pharmacological studies; Drug: metronomic XELOX

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Classic (A); patients recieving classic XELOX (oxaliplatin 130mg/m2 and capecitabine 1000mg/m2 bid)	Drug: Classic XELOX; Other Names: Capecitabine; Oxaliplatin; Other: Blood samples for pharmacological studies; Other Names: No other names
Experimental: metronomic (B); 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.	Other: Blood samples for pharmacological studies; Other Names: No other names; Drug: metronomic XELOX; Other Names: Capecitabine; Oxaliplatin

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

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: June 2, 2020
• First Submitted That Met QC Criteria: June 6, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 6, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: colorectal cancer; metronomic capecitabine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: 201516007.3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO