Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2
Details
Lead Sponsor:
Sidney Kimmel Comprehensive Cancer Center Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins