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Neo-Adjuvant Chemotherapy in Locally Advanced Gastric Cancer

Information source: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Stage T3-4NxM0 Gastric Cancer

Intervention: Capecitabine, doxcetaxol (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Sidney Kimmel Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Alex Chang, Principal Investigator, Affiliation: Johns Hopkins Medicine

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.

Clinical Details

Official title: A Phase II Study of Neo-Adjuvant Chemotherapy in Locally Advanced Gastric Cancer

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Rate of complete pathological response

Secondary outcome:

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.

Feasibility and safety of pre-operative chemotherapy in locally advanced gastric cancer

Correlation of CGH and gene expression profile and their changes after chemotherapy with the same clinical outcomes

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Johns Hopkins Singapore International Medical Center, Singapore 308433, Singapore
Additional Information

Starting date: January 2006
Last updated: December 16, 2008

Page last updated: August 23, 2015

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