* To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin/capecitabine(DCX). * To correlate treatment response with serum RUNX3 promoter hypermethylation. * To determine the toxicities of preoperative DCX * To determine the time to progression/overall survival of preoperative DCX
Background: Pre-operative chemotherapy down size and down stage tumours prior to surgery and improves treatment outcome. However, current chemotherapy regime requires long terrn venous access for protracted chemotherapy infusion. Despite encouraging response rate, there are still a substantial number who did not achieve curative resection after pre-operative chemotherapy. Hence there is a need to develop 1) a more convenient and effective regimen and 2) a surrogate for treatment response so that the non-responder can be identified early. Specific aims: To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin and capecitabine in patients with Stage II \& III gastric or lower oesophageal adenocarcinoma and to correlate treatment response with serum RUNX3 methylation status. Hypotheses: We hypothesize that the proposed preoperative regimen is effective in gastric cancer and can be safely delivered. In addition, RUNX3 promoter hypermethylation status can be a surrogate for treatment response. Methodology: This is a phase II study design to assess the response and tolerability of preoperative docetaxel, cisplatin and capecitabine in patients with operable gastric cancer. Simon's two-stage design is used to calculate the sample size for this Phase II trial, using two levels of response rate, P0 (20%) and P1 (50%). Accordingly, 20 patients is required for this study; 8 patients will be accrued for the first stage followed by 12 more patients when three or more responses are observed during the first stage. The alpha level of the design is 0.04 and power is 0.86. Serum measurement of tumour's RUNX3 promoter hypermethylation will be performed prior to each treatment cycle to evaluate its role as a biomarker for treatment response.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Three cycles of chemotherapy will be administered before surgery with docetaxel at 30 mg/m² on day 1 and 8 in a 21 day treatment cycles.
Three cycles of chemotherapy will be administered before surgery with cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycle.
Three cycles of chemotherapy will be administered before surgery with capecitabine at 750 mg/m² twice daily from day 1 to 14 in a 21 day treatment cycle.
National University Hospital
Singapore, Singapore
Evaluation of Response and Progression using RECIST Criteria
Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques (CT, MRI, x-ray) or as \>10 mm with spiral CT scan.
Time frame: baseline and after two cycles of chemotherapy
Detection of methylated and unmethylated DNA
Treated DNA will be used for PCR using the appropriate primers. Primer sets for RUNX3 will be used for detecting methylated and unmethylated DNA. Results of methylation studies will be analysed and correlated with clinical parameters including age distribution, gender, age, staging, and treatment response. Additional genotyping may be performed on relevant polymorphisms such as XRCC, TS and CYP3A4 to correlate with treatment response.
Time frame: before and after pre-operative chemotherapy (6-8 weeks)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.