Overview

This trial is active, not recruiting.

Condition stage t3-4nxm0 gastric cancer
Treatment capecitabine, doxcetaxol
Phase phase 2
Sponsor Sidney Kimmel Comprehensive Cancer Center
Start date January 2006
Trial size 30 participants
Trial identifier NCT00414271, 05-09-01-04, JS 0420

Summary

Thymidylate Synthase (TS) is a key enzyme in the synthesis of DNA and the target enzyme inhibited by 5-fluorouracil. 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 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 amplized 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 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 (Siewart 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), ALT or 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Rate of complete pathological response
time frame:

Secondary Outcomes

Measure
Correlation of clinical outcomes such as time to recurrence, overall survival, and complete pathological response with RUNX-3 methylation status and Thymidylate synthetase in the tumor tissue.
time frame:
Feasibility and safety of pre-operative chemotherapy in locally advanced gastric cancer
time frame:
Correlation of CGH and gene expression profile and their changes after chemotherapy with the same clinical outcomes
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Age greater than or equal 18 years. Histologic or cytologic diagnosis of adenocarcinoma of stomach or gastric cardia (Siewart 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) greater than or equal 3.5 x 109/L Absolute neutrophil (segmented and bands) count (ANC) greater than or equal 1.5 x 109/L Platelets greater than or equal 100 x 109/L Haemoglobin greater than or equal 9g/dL - Hepatic: Bilirubin within upper limit of normal (ULN), ALT or AST less than or equal 2.5x ULN Alkaline phosphatase less than or equal 2.5x ULN. - Renal: creatinine less than or equal 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. Exclusion Criteria: - Prior treatment for locally advanced or metastatic gastric cancer. Any metastatic disease will render patient ineligible according to AJCC staging manual. (See appendix 11.4). Treatment within the last 30 days with any investigational drug. Concurrent administration of any other cancer therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. Pregnancy. Breast-feeding. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. Poorly controlled diabetes mellitus with fasting blood sugar > 18 mM. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. History of significant neurological or mental disorder, including seizures or dementia. History of hypersensitivity to drugs formulated in Tween 80, the vehicle used for commercial docetaxel formulations. History of hypersensitivity to 5-fluorouracil

Additional Information

Official title A Phase II Study of Neo-Adjuvant Chemotherapy in Locally Advanced Gastric Cancer
Principal investigator Alex Chang
Trial information was received from ClinicalTrials.gov and was last updated in December 2008.
Information provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center.