4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Development and Evaluation of High Risk Group Prediction Model in T1 Stage Renal Cell Cancer Using Molecular Biomarkers

Development and Evaluation of High Risk Group Prediction Model in T1 Stage Renal Cell Cancer Using Molecular Biomarkers

Study Description
Brief Summary:
For the appropriate individualized treatment of T1-stage renal cell carcinoma with heterogeneous biological features, the expression of PBRM1, SETD2, BAP1, KDM5C and the newly proposed FOXC2 and CLIP4, are compared with clinical features. The investigators evaluated the efficacy of FOXC2 and CLIP4 as prognostic biomarkers and developed a high risk prediction model based on these results. In a previous study, the investigators evaluated the efficacy of FOXC2 and CLIP4 as prognostic biomarkers and reported their association with synchronous metastasis in renal cell carcinomas less than 7 cm in size. The investigators analyzed the expression level of renal cell carcinoma according to the size and malignancy (Fuhrman grade) of renal cell carcinoma in T1-stage clear cell type renal cell carcinoma of tumor size less than 7cm. The aim of this study was to analyze the association of tumor recurrence or metastasis, cancer specific survival rate, overall survival rate, tumor size, malignancy and T stage in postoperative biopsy. For expression analysis, PCR amplification and bidirectional Sanger sequencing and mRNA expression analysis (qRT-PCR) were used. For statistical analysis, Fisher exact test, Wilcoxon exact 2-tailed test, Cox proportional hazard regression analysis and competing risk method were used. In this study, the investigators compared the expression of PBRM1, SETD2, BAP1, and KDM5 with newly proposed biomarkers, FOXC2 and CLIP4 and demonstrate the prognostic value of FOXC2 and CLIP4 as new prognostic biomarkers and compared the clinical outcomes with the clinical outcome. Based on these results, the investigators propose a high risk prediction model for individualized treatment of T1-stage renal cell carcinoma. This study is expected to establish a new prediction model and molecular biologic stage for risk stratification of T1-stage renal cell carcinoma patients and apply genetic test for selection of optimal tailored treatment for T1-stage renal cell carcinoma. In addition, it will be an important basic data of the molecular biologic mechanism of metastasis in early renal cell carcinoma and may be used as a basic data for the development and selection of customized therapeutic agents in patients with distant metastasis.

Condition or disease Intervention/treatment
Clear Renal Cell Cancer (< 7cm Size) Procedure: Partial or radical nephrectomy

Show Show detailed description
Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 426 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Development and Evaluation of High Risk Group Prediction Model in T1 Stage Renal Cell Cancer Using Molecular Biomarkers
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : September 22, 2023
Estimated Study Completion Date : September 22, 2023
Arms and Interventions
Group/Cohort Intervention/treatment
Aggressive RCC Group
RCC with synchronous metastasis, recurrence, or cancer-specific death
 Procedure: Partial or radical nephrectomy
The investigators perform partial or radical nephrectomy those diagnosed as RCC.
Non-aggressive RCC Group
RCC without synchronous metastasis, recurrence, or cancer-specific death
 Procedure: Partial or radical nephrectomy
The investigators perform partial or radical nephrectomy those diagnosed as RCC.
Outcome Measures
Primary Outcome Measures :
  1. Assessment of gene expression of biomarkers using reverse-transcription polymerase chain reaction (qRT-PCR) according to groups [ Time Frame: 1 week after the procedure ]
    Assessment of gene expression of biomarkers using reverse-transcription polymerase chain reaction (qRT-PCR) according to groups


Secondary Outcome Measures :
  1. association of tumor size [ Time Frame: 1 week after the procedure ]
    association of tumor size (Fuhrman grade 1-2: low, 3-4: high)

  2. association of tumor malignancy [ Time Frame: 1 week after the procedure ]
    association of tumor malignancy (Fuhrman grade 1-2: low, 3-4: high)


Biospecimen Retention:   Samples Without DNA
FFPE (formalin-fixed paraffin-embedded), frozen tissue, blood, and urine samples

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients who have undergone partial or radical nephrectomy in Severance Hospital(Sinchon) from 2018.11 and 2019.10 were selected.
Criteria

Inclusion Criteria:

  • Patients diagnosed as clear cell renal cell caner T1 stage
  • Patients who have undergone partial or radical nephrectomy in Severance Hospital, Sinchon from 2018.11 and 2019.10
  • Those who agree to give permission to use their human source information
  • Those who agree with this study

Exclusion Criteria:

  • Vulnerable Participants
  • Those who don't agree with this study
Contacts and Locations

Locations
Layout table for location information
Korea, Republic of
Department of Urology, Urological Science Institute, Yonsei University, Colleage of Medicine Recruiting
Seoul, Korea, Republic of, 03722
Contact: Won Sik Ham, MD    82-2-2228-2313    uroham@yuhs.ac   
Sponsors and Collaborators
Yonsei University
Tracking Information
First Submitted Date September 28, 2018
First Posted Date October 3, 2018
Last Update Posted Date September 17, 2019
Actual Study Start Date November 1, 2018
Estimated Primary Completion Date September 22, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 2, 2018) 		Assessment of gene expression of biomarkers using reverse-transcription polymerase chain reaction (qRT-PCR) according to groups [ Time Frame: 1 week after the procedure ]
Assessment of gene expression of biomarkers using reverse-transcription polymerase chain reaction (qRT-PCR) according to groups
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: October 2, 2018)
  • association of tumor size [ Time Frame: 1 week after the procedure ]
    association of tumor size (Fuhrman grade 1-2: low, 3-4: high)
  • association of tumor malignancy [ Time Frame: 1 week after the procedure ]
    association of tumor malignancy (Fuhrman grade 1-2: low, 3-4: high)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Development and Evaluation of High Risk Group Prediction Model in T1 Stage Renal Cell Cancer Using Molecular Biomarkers
Official Title Development and Evaluation of High Risk Group Prediction Model in T1 Stage Renal Cell Cancer Using Molecular Biomarkers
Brief Summary For the appropriate individualized treatment of T1-stage renal cell carcinoma with heterogeneous biological features, the expression of PBRM1, SETD2, BAP1, KDM5C and the newly proposed FOXC2 and CLIP4, are compared with clinical features. The investigators evaluated the efficacy of FOXC2 and CLIP4 as prognostic biomarkers and developed a high risk prediction model based on these results. In a previous study, the investigators evaluated the efficacy of FOXC2 and CLIP4 as prognostic biomarkers and reported their association with synchronous metastasis in renal cell carcinomas less than 7 cm in size. The investigators analyzed the expression level of renal cell carcinoma according to the size and malignancy (Fuhrman grade) of renal cell carcinoma in T1-stage clear cell type renal cell carcinoma of tumor size less than 7cm. The aim of this study was to analyze the association of tumor recurrence or metastasis, cancer specific survival rate, overall survival rate, tumor size, malignancy and T stage in postoperative biopsy. For expression analysis, PCR amplification and bidirectional Sanger sequencing and mRNA expression analysis (qRT-PCR) were used. For statistical analysis, Fisher exact test, Wilcoxon exact 2-tailed test, Cox proportional hazard regression analysis and competing risk method were used. In this study, the investigators compared the expression of PBRM1, SETD2, BAP1, and KDM5 with newly proposed biomarkers, FOXC2 and CLIP4 and demonstrate the prognostic value of FOXC2 and CLIP4 as new prognostic biomarkers and compared the clinical outcomes with the clinical outcome. Based on these results, the investigators propose a high risk prediction model for individualized treatment of T1-stage renal cell carcinoma. This study is expected to establish a new prediction model and molecular biologic stage for risk stratification of T1-stage renal cell carcinoma patients and apply genetic test for selection of optimal tailored treatment for T1-stage renal cell carcinoma. In addition, it will be an important basic data of the molecular biologic mechanism of metastasis in early renal cell carcinoma and may be used as a basic data for the development and selection of customized therapeutic agents in patients with distant metastasis.
Detailed Description
  • collection of FFPE samples: collection of primary or metastatic site
  • micro-dissection: only when the tumor contents are more than 90% are analyzed.

B. Data analysis and model development

  • Development goals - Analysis of prospective biomarker expression in FFPE, and frozen tissue specimens

    - Development of a high-risk prediction model for post-surgical morbidity in T1-stage RCC

    • Contents and scope

      1. Expression analysis of prospective biomarkers in FFPE and frozen tissue samples of T1-stage clear cell type RCC : PBRM1, SETD2, BAP1, and KDM5C expressed as prognostic biomarkers of renal cell carcinoma in other studies

        • The newly proposed FOXC2, CLIP4

          1. Mutational analysis (Transcriptome sequencing with variant calling)

          2. mRNA expression analysis (qRT-PCR) - only when the tumor contents are more than 90% are analyzed.

            - Analysis of tumor size and malignancy as a prognostic predictor of RCC

            - The expression of primary and metastatic lesions was analyzed by considering intratumor heterogeneity in RCC (Fisher exact test, Wilcoxon exact 2-tailed test)

            • Analysis of association with postoperative local recurrence or distant metastasis, cancer-specific survival, and overall survival (Cox proportional hazard regression analysis: Time to recurrence and distant metastasis, overall survival, competing risk method: cancer specific survival)

      2. Development of predictive model for high-risk molecular disease in T1-Stage RCC (survival rate) - elastic net Cox model in glmnet, version 1.7.3

        - prediction accuracy was evaluated using Harrel concordance probability (C-index), internal validation was performed using bootstrap

      3. Development of predictive model for preoperative molecular high risk in T1- Stage RCC (for Poor Pathologic Findings)

        • multivariate logistic/linear regression model
        • prediction accuracy was evaluated using Harrel concordance probability (C-index), internal validation was performed using bootstrap
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
FFPE (formalin-fixed paraffin-embedded), frozen tissue, blood, and urine samples
Sampling Method Non-Probability Sample
Study Population Patients who have undergone partial or radical nephrectomy in Severance Hospital(Sinchon) from 2018.11 and 2019.10 were selected.
Condition Clear Renal Cell Cancer (< 7cm Size)
Intervention Procedure: Partial or radical nephrectomy
The investigators perform partial or radical nephrectomy those diagnosed as RCC.
Study Groups/Cohorts
  • Aggressive RCC Group
    RCC with synchronous metastasis, recurrence, or cancer-specific death
    Intervention: Procedure: Partial or radical nephrectomy
  • Non-aggressive RCC Group
    RCC without synchronous metastasis, recurrence, or cancer-specific death
    Intervention: Procedure: Partial or radical nephrectomy
Publications *
  • Park JS, Jang WS, Kim J, Lee SH, Rha KH, Ham WS. Association between visceral adiposity and DDX11 as a predictor of aggressiveness of small clear-cell renal-cell carcinoma: a prospective clinical trial. Cancer Metab. 2021 Apr 6;9(1):15. doi: 10.1186/s40170-021-00251-y.
  • Park JS, Pierorazio PM, Lee JH, Lee HJ, Lim YS, Jang WS, Kim J, Lee SH, Rha KH, Cho NH, Ham WS. Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers. Cancers (Basel). 2020 Jan 16;12(1). pii: E222. doi: 10.3390/cancers12010222.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 2, 2018) 		426
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 22, 2023
Estimated Primary Completion Date September 22, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients diagnosed as clear cell renal cell caner T1 stage
  • Patients who have undergone partial or radical nephrectomy in Severance Hospital, Sinchon from 2018.11 and 2019.10
  • Those who agree to give permission to use their human source information
  • Those who agree with this study

Exclusion Criteria:

  • Vulnerable Participants
  • Those who don't agree with this study
Sex/Gender
Sexes Eligible for Study: All
Ages 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number NCT03694912
Other Study ID Numbers 4-2018-0753
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: The investigators are going to share study protocol of our study, statistical analysis plan, informed consent form, and clinical study report.
Responsible Party Yonsei University
Study Sponsor Yonsei University
Collaborators Not Provided
Investigators Not Provided
PRS Account Yonsei University
Verification Date September 2019

治疗医院

新药特效药

前沿医讯