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Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer

31. maj 2019 opdateret af: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

  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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

18

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Singapore
      • Singapore, Singapore, 308433
        • Johns Hopkins Singapore International Medical Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: Docetaxel
Docetaxel 60 mg/m2 IV on day 1
Medicin: Capecitabine
Capecitabine 900 mg/m2 PO two times per day from day 1 to day 14 every 3 weeks for 2 cycles.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Pathological Response
Tidsramme: up to 5 years
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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival
Tidsramme: up to 8 years
Median number of months participants alive at the time of observation. Calculated using Kaplan-Meier method.
up to 8 years
Progression-free Survival as Measured by Number of Participants Without Disease Progression.
Tidsramme: up to 5 years
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.
Tidsramme: up to 5 years
Number of participants who experience Grade 3/4 neutropenia, Grade 3 nausea or Grade 3 diarrhea.
up to 5 years
Correlation of CGH and Gene Expression Profile and Their Changes After Chemotherapy With the Same Clinical Outcomes
Tidsramme: up to 5 years
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.
up to 5 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Efterforskere

  • Ledende efterforsker: Alex Chang, Johns Hopkins University

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. januar 2006

Primær færdiggørelse (Faktiske)

1. oktober 2015

Studieafslutning (Faktiske)

1. oktober 2015

Datoer for studieregistrering

Først indsendt

20. december 2006

Først indsendt, der opfyldte QC-kriterier

20. december 2006

Først opslået (Skøn)

21. december 2006

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

25. juli 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. maj 2019

Sidst verificeret

1. maj 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • JS 0420
  • NA_00044000 (Anden identifikator: JHM IRB)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ingen

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

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