Ovarian NeoplasmsNCT04022863
Ovarium Cancer Detection by TEP's and ctDNA
An observational study of Ovarian Neoplasms, run by Gynaecologisch Oncologisch Centrum Zuid at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years, women only
- Conditions the study is for
- Ovarian Neoplasms
- What is being tested?
- TEP and ctDNA
- How many people
- 500 participants
- Where
- 3 sitesNetherlands
- Study dates
- 1 Jul 2019to 1 Dec 2023
- How long will I take part?
- 1 Month
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: all women presenting with an ovarian tumor of unknown nature
Who may be able to join
- Suspicion of ovarian cancer.
Who cannot join
- Previous intraabdominal malignancies in the history
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites, 3 recruiting
- Recruiting
Netherlands Cancer Institute
Amsterdam, North Holland, 1066 CX
Christianne Lok, MD; PhD
- Recruiting
Catharina hospital
Eindhoven, North Brabant, 5623EJ
Jurgen M Piek, MD. PhD., +31(0)40 239 9111, jurgen.piek@catharinaziekenhuis.nl
- Recruiting
Leiden University Medical Center
Leiden, North Holland, 2333 ZA
Cor D de Kroon, MD, PhD
About this study
Official title: Early Detection of Ovarian Cancer and Treatment Response by Tumor Educated Platelets (TEP's) and Circulating Tumor DNA (ctDNA)
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.
Read the 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.
- Conditions
- Ovarian Neoplasms
- Being tested
- TEP, ctDNA
- Keywords
- TEP, ctDNA, ovarian cancer
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEPDiagnostic test
Tumor Educated Platelets
ctDNADiagnostic test
circulating tumor DNA
| Study group | Role | What they receive |
|---|---|---|
| ovarian tumor benign | all pathological proven benign ovarian tumors Receives: Diagnostic Test: TEP; Diagnostic Test: ctDNA | |
| ovarian tumor borderline | all pathological proven borderline ovarian tumors Receives: Diagnostic Test: TEP; Diagnostic Test: ctDNA | |
| ovarian tumor malignant | all pathological proven malignant ovarian tumors Receives: Diagnostic Test: TEP; Diagnostic Test: ctDNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
accuracy of TEP's to determine the nature of an ovarian tumor
Prior to operation blood will be drawn of patients with an ovarian tumor. TEP's will be analysed as described before.
Measured: 1 month
accuracy of ctDNA to determine the nature of an ovarian tumor
Prior to operation blood will be drawn of patients with an ovarian tumor. CtDNA will be analysed as described before.
Measured: 1 month
accuracy of ctDNA to predict treatment response in ovarian cancer
Prior to debulking operation and pre and post chemotherapy ctDNA will be analysed in blood from patients with ovarian cancer as described before.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2019
- Study start1 Jul 2019
- Primary completion1 Jul 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 1 Month
Sponsor and investigators
- Lead sponsor
- Gynaecologisch Oncologisch Centrum Zuid
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, The Netherlands Cancer Institute, Catharina Ziekenhuis Eindhoven, Amsterdam UMC, location VUmc
- Responsible party
- Principal investigator, Jurgen M.J. Piek, Gynaecologisch Oncologisch Centrum Zuid
- Investigators
- Thomas Wurdinger, PhD, Principal investigator, Amsterdam UMC loc VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04022863
- Sponsor's protocol ID
- NL68037.100.18
- Status last verified
- Jul 2019
- First submitted
- 9 Jul 2019
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Ovarian Cancer and Treatment Response by Tumor Educated Platelets (TEP's) and Circulating Tumor DNA (ctDNA)
- ClinicalTrials.gov ID
- NCT04022863
- Acronym / sponsor ID
- NL68037.100.18
- Conditions
- Ovarian Neoplasms
- Keywords
- TEP, ctDNA, ovarian cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Gynaecologisch Oncologisch Centrum ZuidUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, The Netherlands Cancer Institute, Catharina Ziekenhuis Eindhoven, Amsterdam UMC, location VUmc
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 1 Jul 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 17 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Month
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ovarian tumor benign | – | Diagnostic Test: TEP, Diagnostic Test: ctDNAall pathological proven benign ovarian tumors |
| ovarian tumor borderline | – | Diagnostic Test: TEP, Diagnostic Test: ctDNAall pathological proven borderline ovarian tumors |
| ovarian tumor malignant | – | Diagnostic Test: TEP, Diagnostic Test: ctDNAall pathological proven malignant ovarian tumors |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- all women presenting with an ovarian tumor of unknown nature
Key inclusion criteria (1 listed)
- Suspicion of ovarian cancer.
Key exclusion criteria (1 listed)
- Previous intraabdominal malignancies in the history
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TEPTumor Educated Platelets | Diagnostic test | ovarian tumor benign, ovarian tumor borderline, ovarian tumor malignant |
| ctDNAcirculating tumor DNA | Diagnostic test | ovarian tumor benign, ovarian tumor borderline, ovarian tumor malignant |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Wurdinger, PhD principal investigator
Amsterdam UMC loc VUmc
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ovarian Neoplasms, run by Gynaecologisch Oncologisch Centrum Zuid at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jurgen M Piek, MD, PhD (+31(0)40239 9111, jurgen.piek@catharinaziekenhuis.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
accuracy of TEP's to determine the nature of an ovarian tumor (time frame: 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.