Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer
A Phase II Study of Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer
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
- Complete clinical and pathological response rates to pre-operative chemotherapy in locally advanced gastric cancer
- Complete resection rate.
- Time to recurrence, disease free and overall survival
- Correlation of clinical outcome with (Runt-related transcription factor) RUNX-3 methylation status and Thymidylate synthetase in the tumor tissue.
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.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Singapore、シンガポール、308433
- Johns Hopkins Singapore International Medical Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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),
- 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 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Docetaxel and Capecitabine in gastric cancer
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.
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Docetaxel 60 mg/m2 IV on day 1
Capecitabine 900 mg/m2 PO two times per day from day 1 to day 14 every 3 weeks for 2 cycles.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants With Pathological Response
時間枠：up to 5 years
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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.
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up to 5 years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival
時間枠：up to 8 years
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Median number of months participants alive at the time of observation.
Calculated using Kaplan-Meier method.
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up to 8 years
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Progression-free Survival as Measured by Number of Participants Without Disease Progression.
時間枠：up to 5 years
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up to 5 years
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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.
時間枠：up to 5 years
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Number of participants who experience Grade 3/4 neutropenia, Grade 3 nausea or Grade 3 diarrhea.
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up to 5 years
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Correlation of CGH and Gene Expression Profile and Their Changes After Chemotherapy With the Same Clinical Outcomes
時間枠：up to 5 years
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Initially, we also planned to study the thymidylate synthetase expression, methylation of RUNX-3 gene[24] and comprehensive genomic hybridization[25] before and after chemotherapy to look for biomarkers of response and prognostic indication.
But due to the lack of pCR and the small number of patients enrolled, we stopped the correlative studies.
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up to 5 years
|
協力者と研究者
捜査官
- 主任研究者：Alex Chang、Johns Hopkins University
出版物と役立つリンク
便利なリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- JS 0420
- NA_00044000 (その他の識別子：JHM IRB)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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