Clinical trial NCT00414271
Conditions: Stage T3-4NxM0 Gastric Cancer
Keywords: gastric cancer, neo-adjuvant chemotherapy
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2006-01-01; Completion date: 2015-10-01
Enrollment: 18 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Thymidylate Synthase (TS) is a key enzyme in the synthesis of DNA and the target enzyme inhibited by 5-fluorouracil (5-FU). TS level in the tumour cells has been reported as predictive to response to 5-FU and a prognostic factor in colorectal and gastric cancer patients. We plan to study TS by immunohistochemistry (IHC) in the paraffin blocks of tumour tissue.

A combined comparative genomic hybridization (CGH) and expression microarray analysis of gastric cancer specimens before and after neoadjuvant chemotherapy. CGH will be performed using standard technique routinely done in Dr Patrick Tan's laboratory at the National Cancer Centre, which determines the gain or loss of DNA copies of each chromosome. Total RNA will be extracted from at least one biopsy sample which contains at least 50% cancer cells by homogenization of the tumour tissue and tri-sol method. 5 ug of RNA were amplified and hybridized with the C-DNA microarrays of 18K targets.

Primary Objective 1. Feasibility and safety of pre-operative chemotherapy in locally advanced gastric cancer.

Secondary Objective

1. Complete clinical and pathological response rates to pre-operative chemotherapy in locally advanced gastric cancer
2. Complete resection rate.
3. Time to recurrence, disease free and overall survival
4. Correlation of clinical outcome with (Runt-related transcription factor) RUNX-3 methylation status and Thymidylate synthetase in the tumor tissue.
5. Correlation of CGH and gene expression profile and their changes after chemotherapy with clinical outcome.

   Patients may be included in the study only if they meet all of the following criteria:

   Age at least 18 years. Histologic or cytologic diagnosis of adenocarcinoma of stomach or gastric cardia (Siewert Classification Type III) Preoperative Stage T3-4NxM0 by endoscopic ultrasound, CT of the abdomen/pelvis and laparoscopy. (CT of the chest if it is a cardia lesion).

   Absence of malignant cells in peritoneal lavage fluid during laparoscopic examination.

   Patients must not have received any prior chemotherapy or hormonal therapy for the treatment of gastric cancer.

   Karnofsky performance status of 70 or higher. Estimated life expectancy of at least 12 weeks.

   Adequate organ function including the following:

   \- Bone marrow: White blood cells (WBC) at least 3.5 x 109/L Absolute neutrophil (segmented and bands) count (ANC) at least 1.5 x 109/L Platelets at least 100 x 109/L Haemoglobin at least 9g/dL

   \- Hepatic: Bilirubin within upper limit of normal (ULN), Aspartate transaminase (ALT) or Alanine transaminase (AST) not more than 2.5x ULN Alkaline phosphatase not more than 2.5x ULN.

   \- Renal: creatinine not more than 1.5x ULN Signed informed consent by patient or legal representative. Patients with reproductive potential must use an approved contraceptive method if appropriate (eg, intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

   The study plans to recruit 30 patients in 12-18 months.

Detailed description:

Arms: arm 1: Intravenous docetaxel 60 mg/m2 on day 1 and oral capecitabine 900 mg/m2 two times per day from day 1 to day 14 every 3 weeks for 2 cycles.
Interventions: intervention 1: Docetaxel intervention 2: Capecitabine
Intervention descriptions: intervention 1: Docetaxel 60 mg/m2 IV on day 1 intervention 2: Capecitabine 900 mg/m2 PO two times per day from day 1 to day 14 every 3 weeks for 2 cycles.

Protocol documents: