Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer

NCT00414271 | Completed Phase 2 Results

• 2 other identifiers: JS 0420NA_00044000
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Stage T3-4NxM0 Gastric Cancer

Keywords

gastric cancer, neo-adjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Pathological Response

  Number of participants who completed neoadjuvant chemotherapy and underwent repeat CT and endoscopic ultrasound (EUS) with pathological complete response (pCR), partial response in the primary tumor, stable disease or progressive disease as defined by EUS criteria.

  up to 5 years

Secondary Outcomes (4)

• Overall Survival

  up to 8 years

• Progression-free Survival as Measured by Number of Participants Without Disease Progression.

  up to 5 years

• Feasibility and Safety of Pre-operative Chemotherapy in Locally Advanced Gastric Cancer as Assessed by Number of Participants Who Experienced Adverse Events Grade 3 or Higher as Defined by CTCAE.

  up to 5 years

• Correlation of CGH and Gene Expression Profile and Their Changes After Chemotherapy With the Same Clinical Outcomes

  up to 5 years

Study Arms (1)

Docetaxel and Capecitabine in gastric cancer

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Capecitabine

Interventions

Docetaxel DRUG

Docetaxel 60 mg/m2 IV on day 1

Docetaxel and Capecitabine in gastric cancer

Capecitabine DRUG

Capecitabine 900 mg/m2 PO two times per day from day 1 to day 14 every 3 weeks for 2 cycles.

Docetaxel and Capecitabine in gastric cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal 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) 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),

You may not qualify if:

• Prior treatment for locally advanced or metastatic gastric cancer. Any metastatic disease will render patient ineligible according to American Joint Committee on Cancer (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 mmol/L(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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Singapore International Medical Center

Singapore, 308433, Singapore

Location

Related Publications (1)

• Chang AY, Foo KF, Koo WH, Ong S, So J, Tan D, Lim KH. Phase II study of neo-adjuvant chemotherapy for locally advanced gastric cancer. BMJ Open Gastroenterol. 2016 Aug 23;3(1):e000095. doi: 10.1136/bmjgast-2016-000095. eCollection 2016.

  PMID: 27648294 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Docetaxel; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Prof Alex Chang
• Organization: Johns Hopkins Singapore

alexchang@imc.jhmi.edu

+65 68802220

Study Officials

• Alex Chang

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2006
• First Posted: December 21, 2006
• Study Start: January 1, 2006
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 25, 2019
• Results First Posted: July 25, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)