Effect of Capecitabine as Maintenance Therapy Versus Observation on Patients With Early Stage Triple Negative Breast Cancer
Phase: PHASE2
Conditions: Triple -Negative Breast Cancer
Sponsor: Beni-Suef University

Effect of Capecitabine as Maintenance Therapy versus observation on patients with early stage 
triple negative breast cancer 
 
 
1/10/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Introduction 
The poor prognosis of triple-negative breast cancer (TNBC) results from a lack of available 
targeted treatment options coupled with the aggressive biological behavior of this subtype, 
which is associated with a high risk of early recurrence, particularly visceral metastasis.1,2 
However, chemotherapy is the only adjuvant treatment option for patients with early-stage 
TNBC. Effective maintenance therapies to reduce the risk of relapse and death are needed. 
Chemotherapy using lower dosage and higher frequency is thought to exert its anticancer 
activity by targeting 2 mechanisms of metastasis: angiogenesis and immune escape.3 Therefore, 
low-dose chemotherapy might prevent TNBC from metastasizing. 
Capecitabine, an orally administered chemotherapeutic drug used widely in the treatment of 
metastatic breast cancer, is a potential candidate therapy for low-dose administration as 
maintenance to prevent recurrence.4-6 
Several previous clinical trials added high-dose capecitabine to standard breast cancer adjuvant 
chemotherapy regimens and have reported conflicting results,7-11 In this study, was designed 
to evaluate the effect of low-dose capecitabine maintenance therapy after completion of 
standard adjuvant treatment on disease-free and overall survival in women with early-stage 
TNBC. 
Aim of the work 
The aim of work is to compare the efficacy and adverse events of low-dose capecitabine 
maintenance with observation following standard adjuvant treatment in patients with early-
stage TNBC attend to oncology department, Beni- seuf university. 
Study design 
This study is a randomized, phase 2 clinical trial study and will be enrolled at clinical oncology 
department, Faculty of medicine, Beni-Suef University . 
The study  will investigate the effect of low dose and high frequency of receiving capecitabine as 
maintenance therapy in patients with low risk triple negative breast cancer.  
Methods 
Eligible patients will randomly open label assigned in a 1:1 ratio to receive either low-dose 
capecitabine maintenance (intervention group) which is newly diagnostic to be planned to 
receive capecitabine after finishing the standard adjuvant treatment or observation (control 
group) within 4 weeks after completion of standard adjuvant chemotherapy. 
The capecitabine maintenance group will receive oral capecitabine at 650 mg/m2, twice daily 
continuously for 1 year. 

Total follow up of the study is 2 years, one year for drug receving with monthy follow up for 
adverse effect and the other year for every 3 months follow up to asses DFS and OS. 
Collection of capecitabine dose will receive and adverse events will assessed monthly during 
capecitabine maintenance in the capecitabine group. In both groups, physical examination, 
assessment of menopausal status, breast ultrasound, and abdominal ultrasound were 
performed every 3 months during 2 years of follow up; mammography and chest x-ray were 
performed yearly. Patients who has not experienced recurrence or death at the time of data 
analysis will censored as alive and event-free at the date of last follow-up.  
Sample size 
Sample size was calculated based on online openepi calculator. We calculated the required 
sample size to detect a statistically significant difference in AE rates between groups using a 
two-sided chi-square test. Therefore, our planned enrollment of 80 patients (40 per group) is 
sufficient to detect clinically meaningful differences in treatment-emergent adverse events. 
Inclusion criteria 
Eligible trial participants will women who has 
1. Pathologically confirmed invasive breast ductal carcinoma 
2. Hormone receptor negative (<1% positive cells by immunohistochemistry staining) and ERBB2 
negative.  
3. Participants had early-stage tumors that were stage T1b-3N0-3cM0, without positive 
supraclavicular or internal mammary lymph node involvement based on the American Joint 
Committee on Cancer (AJCC 2010, seventh edition) staging criteria. 
4. They received standard treatments, including modified radical mastectomy or breast-
conserving surgery, neo-/adjuvant chemotherapy, and radiotherapy according to institutional 
guidelines. 
Exclusion criteria 
Key exclusion criteria will include 
1. Inflammatory or bilateral breast cancer. 
2. History of invasive breast cancer or other malignancies; receipt of other biologic agents or 
immunotherapy. 
3. Lactation or pregnancy; or severe coexisting illness. 
Study end points 

The primary end point of the study is to assess the adverse effects of the Capecitabine after 6 
months after starting treatment. 
Secondary end points will include 
1. Disease-free survival, defined as the time from randomization to the first occurrence of the 
following events: local relapse, distant metastasis or contralateral breast cancer. 
2. overall survival (the time from randomization to death from any cause). 
3. Adverse events were assessed and graded according to the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events version 4.0. Hand-foot syndrome (a common 
adverse effect of the fluoropyrimidine chemotherapy agent capecitabine) events will graded 
from 1 to 3.  
Statistical Analysis: 
For statistical analysis, all data will recorded and analyzed .The p-value reports will two tailed 
and an alpha level of 0.05 was used to assess statistical significance. Time-to-event curves will 
be described using the Kaplan-Meier method. A Cox proportional hazards model will be used to 
estimate and test the treatment effect. Analysis of the interaction between treatment effects 
and selected subgroups will conducted using a χ2 test for heterogeneity and described with 
forest plots. Q statistics and I2 values will be used to assess the potential heterogeneity of trial-
specific Disease-Free Survival.The data will be coded and entered using: the statistical package 
for social science version 22 (SPSS v 22).For descriptive analysis of the result,the data will be 
summarized using (minimum, maximum, mean and standard deviation) for quantitative data 
and the frequency distribution for qualitative data.Student t- test: for comparison between 
means of two groups of quantitative variables.Paired sample t-test will be used for comparison 
between means of paired quantitative variables.Chi square test: for comparison between two 
groups of categorical data or frequency of events.  
P: The probability/significance value 
P value ≥0.05: Not significant 
P value <0.05: Significant 
The Correlation coefficient (r):A positive correlation coefficient means that as the value of one 
variable increases, the value of the other variable increases; as one decreases the other 
decreases. A negative correlation coefficient indicates that as one variable increases, the other 
decreases, and vice-versa.Graphic presentations in this study will done by: means of “Microsoft 
excel version 2007. 
Ethical considerations: 

This study will be approved by faculty of Medicine; Beni-Suef university research Ethics 
committee (FBBSU-REC)which adhered to principles of the Declaration of Helsinki. Informed 
consents will be signed from the participants, after explanation of the study to all participants. 
 
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