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 / Ovarium Cancer Detection by TEP's and ctDNA

Ovarium Cancer Detection by TEP's and ctDNA

Study Description
Brief Summary:
Rationale: Cancer is primarily diagnosed by clinical presentation, imaging and pathological analysis of tissue biopsies, increasingly supported by molecular diagnostics tests. However, late diagnosis and misdiagnosis due to limitations of tissue biopsy acquisition remains a major problem. Therefore, a general blood test to pinpoint cancer early and adequately can be considered the 'Holy Grail', because diagnosis in an earlier stage significantly improves the chance of cure from cancer. Several blood-based sources are currently being evaluated as liquid biopsies, including circulating tumor (ct) DNA and circulating tumor cells, but none of these have been implemented for primary (multiclass) cancer diagnostics. Protein tumor markers have been used for decades in diagnosis and monitoring of treatment response in different cancers. Tumor-educated platelets (TEPs) can function as potential blood-based source for (early) cancer diagnostics. Blood platelets are implicated in hemostasis and wound healing. Platelets have recently emerged as central players and immediate responders in the systemic and local responses to tumor growth. Confrontation of platelets by tumor cells via transfer of tumor-associated molecules ('education') results in the sequestration of these molecules (derived from both tumor and its micro-environment), causing a distinct platelet messenger Ribonucleic acid (mRNA) profile. We have previously shown that platelets acquire glioblastoma and prostate cancer mRNA biomarkers and that glioblastoma TEP mRNA profiles harbour diagnostic potential. Furthermore, circulating tumor desoxyrubonucleic acid (ctDNA) has recently been implicated as biomarker for therapy effectiveness and survival. Objective: develop and evaluate the potential of combination of tumor markers, TEPs and ctDNA as liquid biomarkers for (early) ovarium cancer diagnostics and as markers for therapy response and survival. Study design: investigator-initiated, longitudinal, observational study. Study population: patients suspected of having ovarium cancer and are therefore planned for surgery. Main study parameters/endpoints: The difference in biomarker profile from benign ovarium lesions versus cancerous lesions. Nature and extent of the burden and risks associated with participation, benefit and group relatedness. There is no extra burden/risk for the patients in this study. Three extra vials of blood.

Condition or disease Intervention/treatment
Ovarian Neoplasms Diagnostic Test: TEP Diagnostic Test: ctDNA

Detailed Description:
Cancer is primarily diagnosed by clinical presentation, radiology, biochemical tests and pathological analysis of tumor tissue, increasingly supported by molecular diagnostic tests. Molecular profiling of tumor tissue samples has emerged as a potential cancer classifying method. In order to overcome limitations of tissue acquisition the use of blood-based liquid biopsies has been suggested. Several blood-based sources are currently being evaluated as liquid biopsies, including plasma DNA and circulating tumor cells. So far, implementation of liquid biopsies for early detection of cancer has been hampered by non-specificity of these sources to pinpoint the nature of the primary tumor. It has been reported that tumor-educated platelets (TEPs) may enable blood-based cancer diagnostics. Platelets are circulating anucleated cell fragments that originate from megakaryocytes in bone marrow, and are traditionally known for their role in hemostasis and initiation of wound healing. More recently, platelets have emerged as central players in the systemic and local responses to tumor growth. Confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules ('education') is an emerging concept and results in the sequestration of such biomolecules. Moreover, external stimuli, such as activation of platelet surface receptors and lipopolysaccharide-mediated platelet activation induce specific splicing of pre-mRNAs in circulating platelets. Platelets may also undergo queue-specific splice events in response to signals released by cancer cells and the tumor microenvironment -such as stromal and immune cells-. The combination of specific splice events in response to external signals and the capacity of platelets to directly ingest (spliced) circulating mRNA can provide TEPs with a highly dynamic mRNA repertoire, with potential applicability to cancer diagnostics. Additionally, the value of other biomarkers that can be derived from a liquid biopsy will be tested in this study. In addition, recently a hallmark paper has shown that combinations of protein tumor markers and ctDNA analysis could discriminate persons with different types of cancer from healthy controls with on average 70% sensitivity (at 99% specificity). In the case of ovarium cancer the sensitivity was 98%. Obvious advantages of liquid biopsy compared to tissue biopsy is the easy accessibility of the material to be obtained and the fact that tumor derived material in blood may cover the cancer heterogeneity where a tissue biopsy is limited to the alterations in the tumor punctured. Therefore, this study investigates the clinical value of longitudinal assessment of liquid biopsy-derived information in diagnosis and monitoring of treatment response in patients suspected of ovarian cancer.
Study Design
Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 1 Month
Official Title: Early Detection of Ovarian Cancer and Treatment Response by Tumor Educated Platelets (TEP's) and Circulating Tumor DNA (ctDNA)
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : December 1, 2023
Arms and Interventions
Group/Cohort Intervention/treatment
ovarian tumor benign
all pathological proven benign ovarian tumors
Diagnostic Test: TEP
Tumor Educated Platelets

Diagnostic Test: ctDNA
circulating tumor DNA

ovarian tumor borderline
all pathological proven borderline ovarian tumors
Diagnostic Test: TEP
Tumor Educated Platelets

Diagnostic Test: ctDNA
circulating tumor DNA

ovarian tumor malignant
all pathological proven malignant ovarian tumors
Diagnostic Test: TEP
Tumor Educated Platelets

Diagnostic Test: ctDNA
circulating tumor DNA

Outcome Measures
Primary Outcome Measures :
  1. accuracy of TEP's to determine the nature of an ovarian tumor [ Time Frame: 1 month ]
    Prior to operation blood will be drawn of patients with an ovarian tumor. TEP's will be analysed as described before.

  2. accuracy of ctDNA to determine the nature of an ovarian tumor [ Time Frame: 1 month ]
    Prior to operation blood will be drawn of patients with an ovarian tumor. CtDNA will be analysed as described before.

  3. accuracy of ctDNA to predict treatment response in ovarian cancer [ Time Frame: 1 month ]
    Prior to debulking operation and pre and post chemotherapy ctDNA will be analysed in blood from patients with ovarian cancer as described before.


Biospecimen Retention:   Samples With DNA
Tumor educated platelets circulating tumor DNA

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   women with ovarian tumors
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
all women presenting with an ovarian tumor of unknown nature
Criteria

Inclusion Criteria:

  • Suspicion of ovarian cancer.

Exclusion Criteria:

  • Previous intraabdominal malignancies in the history
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Jurgen M Piek, MD, PhD +31(0)40239 9111 jurgen.piek@catharinaziekenhuis.nl
Contact: Volkher Scharnhorst, MD, PhD +31(0)40239 9111 volkher.scharnhorst@catharinaziekenhuis.nl

Locations
Layout table for location information
Netherlands
Catharina hospital Recruiting
Eindhoven, Brabant, Netherlands, 5623EJ
Contact: Jurgen M Piek, MD. PhD.    +31(0)40 239 9111    jurgen.piek@catharinaziekenhuis.nl   
Netherlands Cancer Institute Recruiting
Amsterdam, Noord Holland, Netherlands, 1066 CX
Contact: Christianne Lok, MD; PhD         
Leiden University Medical Center Recruiting
Leiden, Noord Holland, Netherlands, 2333 ZA
Contact: Cor D de Kroon, MD, PhD         
Sponsors and Collaborators
Gynaecologisch Oncologisch Centrum Zuid
Leiden University Medical Center
The Netherlands Cancer Institute
Catharina Ziekenhuis Eindhoven
VU University Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Thomas Wurdinger, PhD Amsterdam UMC loc VUmc
Tracking Information
First Submitted Date July 9, 2019
First Posted Date July 17, 2019
Last Update Posted Date July 17, 2019
Actual Study Start Date July 1, 2019
Estimated Primary Completion Date July 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 14, 2019)
  • accuracy of TEP's to determine the nature of an ovarian tumor [ Time Frame: 1 month ]
    Prior to operation blood will be drawn of patients with an ovarian tumor. TEP's will be analysed as described before.
  • accuracy of ctDNA to determine the nature of an ovarian tumor [ Time Frame: 1 month ]
    Prior to operation blood will be drawn of patients with an ovarian tumor. CtDNA will be analysed as described before.
  • accuracy of ctDNA to predict treatment response in ovarian cancer [ Time Frame: 1 month ]
    Prior to debulking operation and pre and post chemotherapy ctDNA will be analysed in blood from patients with ovarian cancer as described before.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Ovarium Cancer Detection by TEP's and ctDNA
Official Title Early Detection of Ovarian Cancer and Treatment Response by Tumor Educated Platelets (TEP's) and Circulating Tumor DNA (ctDNA)
Brief Summary Rationale: Cancer is primarily diagnosed by clinical presentation, imaging and pathological analysis of tissue biopsies, increasingly supported by molecular diagnostics tests. However, late diagnosis and misdiagnosis due to limitations of tissue biopsy acquisition remains a major problem. Therefore, a general blood test to pinpoint cancer early and adequately can be considered the 'Holy Grail', because diagnosis in an earlier stage significantly improves the chance of cure from cancer. Several blood-based sources are currently being evaluated as liquid biopsies, including circulating tumor (ct) DNA and circulating tumor cells, but none of these have been implemented for primary (multiclass) cancer diagnostics. Protein tumor markers have been used for decades in diagnosis and monitoring of treatment response in different cancers. Tumor-educated platelets (TEPs) can function as potential blood-based source for (early) cancer diagnostics. Blood platelets are implicated in hemostasis and wound healing. Platelets have recently emerged as central players and immediate responders in the systemic and local responses to tumor growth. Confrontation of platelets by tumor cells via transfer of tumor-associated molecules ('education') results in the sequestration of these molecules (derived from both tumor and its micro-environment), causing a distinct platelet messenger Ribonucleic acid (mRNA) profile. We have previously shown that platelets acquire glioblastoma and prostate cancer mRNA biomarkers and that glioblastoma TEP mRNA profiles harbour diagnostic potential. Furthermore, circulating tumor desoxyrubonucleic acid (ctDNA) has recently been implicated as biomarker for therapy effectiveness and survival. Objective: develop and evaluate the potential of combination of tumor markers, TEPs and ctDNA as liquid biomarkers for (early) ovarium cancer diagnostics and as markers for therapy response and survival. Study design: investigator-initiated, longitudinal, observational study. Study population: patients suspected of having ovarium cancer and are therefore planned for surgery. Main study parameters/endpoints: The difference in biomarker profile from benign ovarium lesions versus cancerous lesions. Nature and extent of the burden and risks associated with participation, benefit and group relatedness. There is no extra burden/risk for the patients in this study. Three extra vials of blood.
Detailed Description Cancer is primarily diagnosed by clinical presentation, radiology, biochemical tests and pathological analysis of tumor tissue, increasingly supported by molecular diagnostic tests. Molecular profiling of tumor tissue samples has emerged as a potential cancer classifying method. In order to overcome limitations of tissue acquisition the use of blood-based liquid biopsies has been suggested. Several blood-based sources are currently being evaluated as liquid biopsies, including plasma DNA and circulating tumor cells. So far, implementation of liquid biopsies for early detection of cancer has been hampered by non-specificity of these sources to pinpoint the nature of the primary tumor. It has been reported that tumor-educated platelets (TEPs) may enable blood-based cancer diagnostics. Platelets are circulating anucleated cell fragments that originate from megakaryocytes in bone marrow, and are traditionally known for their role in hemostasis and initiation of wound healing. More recently, platelets have emerged as central players in the systemic and local responses to tumor growth. Confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules ('education') is an emerging concept and results in the sequestration of such biomolecules. Moreover, external stimuli, such as activation of platelet surface receptors and lipopolysaccharide-mediated platelet activation induce specific splicing of pre-mRNAs in circulating platelets. Platelets may also undergo queue-specific splice events in response to signals released by cancer cells and the tumor microenvironment -such as stromal and immune cells-. The combination of specific splice events in response to external signals and the capacity of platelets to directly ingest (spliced) circulating mRNA can provide TEPs with a highly dynamic mRNA repertoire, with potential applicability to cancer diagnostics. Additionally, the value of other biomarkers that can be derived from a liquid biopsy will be tested in this study. In addition, recently a hallmark paper has shown that combinations of protein tumor markers and ctDNA analysis could discriminate persons with different types of cancer from healthy controls with on average 70% sensitivity (at 99% specificity). In the case of ovarium cancer the sensitivity was 98%. Obvious advantages of liquid biopsy compared to tissue biopsy is the easy accessibility of the material to be obtained and the fact that tumor derived material in blood may cover the cancer heterogeneity where a tissue biopsy is limited to the alterations in the tumor punctured. Therefore, this study investigates the clinical value of longitudinal assessment of liquid biopsy-derived information in diagnosis and monitoring of treatment response in patients suspected of ovarian cancer.
Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 1 Month
Biospecimen Retention:   Samples With DNA
Description:
Tumor educated platelets circulating tumor DNA
Sampling Method Non-Probability Sample
Study Population all women presenting with an ovarian tumor of unknown nature
Condition Ovarian Neoplasms
Intervention
  • Diagnostic Test: TEP
    Tumor Educated Platelets
  • Diagnostic Test: ctDNA
    circulating tumor DNA
Study Groups/Cohorts
  • ovarian tumor benign
    all pathological proven benign ovarian tumors
    Interventions:
    • Diagnostic Test: TEP
    • Diagnostic Test: ctDNA
  • ovarian tumor borderline
    all pathological proven borderline ovarian tumors
    Interventions:
    • Diagnostic Test: TEP
    • Diagnostic Test: ctDNA
  • ovarian tumor malignant
    all pathological proven malignant ovarian tumors
    Interventions:
    • Diagnostic Test: TEP
    • Diagnostic Test: ctDNA
Publications * Not Provided

*   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: July 14, 2019)
500
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 1, 2023
Estimated Primary Completion Date July 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Suspicion of ovarian cancer.

Exclusion Criteria:

  • Previous intraabdominal malignancies in the history
Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: women with ovarian tumors
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Jurgen M Piek, MD, PhD +31(0)40239 9111 jurgen.piek@catharinaziekenhuis.nl
Contact: Volkher Scharnhorst, MD, PhD +31(0)40239 9111 volkher.scharnhorst@catharinaziekenhuis.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT04022863
Other Study ID Numbers NL68037.100.18
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
Responsible Party Jurgen M.J. Piek, Gynaecologisch Oncologisch Centrum Zuid
Study Sponsor Gynaecologisch Oncologisch Centrum Zuid
Collaborators
  • Leiden University Medical Center
  • The Netherlands Cancer Institute
  • Catharina Ziekenhuis Eindhoven
  • VU University Medical Center
Investigators
Principal Investigator: Thomas Wurdinger, PhD Amsterdam UMC loc VUmc
PRS Account Gynaecologisch Oncologisch Centrum Zuid
Verification Date July 2019

治疗医院