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Ovarium Cancer Detection by TEP's and ctDNA

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ClinicalTrials.gov Identifier: NCT04022863
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborators:
Leiden University Medical Center
The Netherlands Cancer Institute
Catharina Ziekenhuis Eindhoven
VU University Medical Center
Information provided by (Responsible Party):
Jurgen M.J. Piek, Gynaecologisch Oncologisch Centrum Zuid

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.

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

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




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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04022863


Contacts
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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
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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
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Principal Investigator: Thomas Wurdinger, PhD Amsterdam UMC loc VUmc

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Responsible Party: Jurgen M.J. Piek, principal investigator, Gynaecologisch Oncologisch Centrum Zuid
ClinicalTrials.gov Identifier: NCT04022863     History of Changes
Other Study ID Numbers: NL68037.100.18
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jurgen M.J. Piek, Gynaecologisch Oncologisch Centrum Zuid:
TEP
ctDNA
ovarian cancer

Additional relevant MeSH terms:
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Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders