Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06445621
Status:
RECRUITING
Last Update Posted:
2024-06-06
First Post:
2024-05-23
Brief Title:
Early Detection of Relapse in Ovarian Cancer Using Capillary Home-sampling and a Protein Biomarker Test
Sponsor:
Uppsala University Hospital
Organization:
Uppsala University Hospital
Study Overview
Official Title:
Early Detection of Relapse in Ovarian Cancer Using Capillary Home-sampling and a Multiplex Protein Biomarker Test - a Pilot Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FOLL-OV
Brief Summary:
PURPOSEAIMS There is no consensus on optimal follow-up after ovarian cancer A recent study demonstrated eight months prolonged survival in patients with complete surgical resection Hence it is crucial to detect relapses early when the tumor burden is limited
The research group have previously identified a plasma protein panel with high accuracy in detecting ovarian cancer at diagnosis and follow-up The aim with this feasibility study is to validate the panel for its capacity to detect early relapse in symptom-free patients in a user-friendly non-invasive way ie a home-administered capillary sampling The results will be the foundation for a forthcoming national prospective randomized trial
METHODS The study is designed as a prospective cohort study including women in the control program after ovarian cancer in Uppsala and Umeå Sweden The study participants should have no evidence of disease after primary treatment or after relapse In addition to standard follow-up they will be asked to take a capillary home-sample blood-test from finger every second month during one year or until relapse The result of the test will not affect treatment but solely be used for research purposes
IMPORTANCE The study aims to clarify following issues
1 Calibration of the risk score in capillary blood samples
2 Evaluation of the logistics in home-sampling
3 Evaluation of the acceptability reasons of drop-out etc of home-sampling by structured interviews of a sample of study participants
CLINICAL SIGNIFICANCE The hypothesis behind the study is that more frequent analysis of a protein panel specific for ovarian cancer will lead to earlier detection of relapse earlier treatment and a better prognosis Additionally in the future the vision is that women may choose between different ways of follow-up depending on individual risk factors personal preferences and logistic reasons In the long-term the results of the applicability of home-administered blood sampling from this study can be useful in other patient groups as well
The research group have previously identified a plasma protein panel with high accuracy in detecting ovarian cancer at diagnosis and follow-up The aim with this feasibility study is to validate the panel for its capacity to detect early relapse in symptom-free patients in a user-friendly non-invasive way ie a home-administered capillary sampling The results will be the foundation for a forthcoming national prospective randomized trial
METHODS The study is designed as a prospective cohort study including women in the control program after ovarian cancer in Uppsala and Umeå Sweden The study participants should have no evidence of disease after primary treatment or after relapse In addition to standard follow-up they will be asked to take a capillary home-sample blood-test from finger every second month during one year or until relapse The result of the test will not affect treatment but solely be used for research purposes
IMPORTANCE The study aims to clarify following issues
1 Calibration of the risk score in capillary blood samples
2 Evaluation of the logistics in home-sampling
3 Evaluation of the acceptability reasons of drop-out etc of home-sampling by structured interviews of a sample of study participants
CLINICAL SIGNIFICANCE The hypothesis behind the study is that more frequent analysis of a protein panel specific for ovarian cancer will lead to earlier detection of relapse earlier treatment and a better prognosis Additionally in the future the vision is that women may choose between different ways of follow-up depending on individual risk factors personal preferences and logistic reasons In the long-term the results of the applicability of home-administered blood sampling from this study can be useful in other patient groups as well
Detailed Description:
Early detection of relapse in ovarian cancer using capillary home-sampling and a multiplex protein biomarker test - a pilot study
PURPOSE AND AIMS Epithelial ovarian cancer EOC is the deadliest of all gynecologic cancers with 700 incident cases per year in Sweden Even though almost three out of four women with EOC relapse within 2-3 years there is a striking lack of prospective trials on optimized follow-up after EOC treatment The research group have previously identified a plasma marker protein panel with high accuracy for ovarian cancer diagnosis and follow-up The aim with this pilot study is to validate the protein panel for its capacity to detect early relapse in symptom-free patients in a user-friendly non-invasive way ie a home-administered capillary sampling Further the results will be the foundation for a forthcoming national prospective randomized trial RCT - the FOLL-OV trial
SURVEY OF THE FIELDPRELIMINARY RESULTS One of the main purposes with a follow-up program is to find cancer relapse at an early stage and thereby improve the patients chance of successful treatment and prolonged survival Yet there is a striking lack of prospective studies in the field
A recent RCT demonstrated eight months prolonged overall survival when treated with surgery at first relapse compared to chemotherapy alone however the survival benefit was limited to women where complete surgical resection was achieved 3 Hence it has become more important than ever to detect relapse as soon as realistically possible when the tumor burden is limited
As of present the Swedish National Guidelines for EOC recommend follow-up 3-4 timesyear during the first two years after completed treatment The follow-up consists of physical and gynecologic examination transvaginal ultrasound and is many times complemented with the EOC biomarker CA125 but this is optional CA125 is an unspecific marker and not elevated in all types of EOC In a Cochrane review evaluating follow-up strategies of women with EOC only one RCT was included and thus further RCTs are needed to evaluate different types of follow-up strategies using outcomes such as survival quality of life QoL cost and psychological effects Importantly in two recent retrospective studies almost no relapses were detected exclusively on physical examination and the need for regular in-clinic visits were questioned in favor of virtual meetings with a review of symptoms and measurements of tumor marker
Clearly better biomarkers for EOC relapse are needed The research group have recently developed a risk score for detection of EOC based on analysis of 11 plasma proteins When validated in two independent clinical cohorts this assay showed a sensitivity of 083091 and specificity of 088092 for separating EOC and histology benign conditions Further we have demonstrated the possibility to track changes in relation to treatment outcome and relapse using the same risk score Using machine learning four distinct risk score trajectories are defined that indicate that it could be possible to detect relapse events up to 60 days prior to the first clinically recorded event These results were conducted using wet plasma but previous investigations show that dried blood spots work well for proteomics analyses with the intended assay PEA although a re-calibration of the risk-score is needed to accommodate differences between the dry and wet format
This pilot study as part of a larger clinical research project aims to re-calibrate the risk-score and to assess it in a clinical setting using a home-based capillary blood sampling
AIMS OUTCOME
The pilot study will be designed as a prospective cohort study with aim to clarify following questions before planning of a national RCT
Calibrationvalidation of the risk score in capillary blood samples
Accuracy of monthly home-sampling and standard Ca125 for diagnosis of relapse
Evaluate the logistics in home-sampling patients instructions registration communication etc
Evaluate the acceptability of home-sampling by semi-structured interviews of a sample of study participants reasons of drop-out communication aspects pros and cons with repeated sampling
METHOD The pilot study will be designed as a prospective cohort study
Study population
Inclusion criteria
18 years of age
Included in the control program for ovarianfallopianprimary peritoneal cancer at Uppsala University Hospital or at Norrlands University Hospital Sweden
Within 3 years after completed primary treatment for stage III-IV EOC or after treatment for relapse
No evidence of disease normal CA 125 and no tumor detected on radiology or clinical examination
Patients on maintenance therapy PARP-inhibitor bevazicumab can be included
Exlusion Other cancer diagnosis within 2 years except squamous skin cancer or basalioma Non-Swedish speaking Not able to understand instructions
Intervention The participants will follow the standard follow-up program with scheduled visit 3-4 timesyear The follow-up consists of physical and gynecologic examination transvaginal ultrasound and sampling of s-CA125
At inclusion the participants will receive written information and sign informed consent
Capillary test
Study participants will be asked to take a capillary blood sample
at inclusion with assistance from study nurse
at home monthly during one year or until relapse
at suspicion of relapse The capillary sample and sent in to the laboratory in an envelope provided to the study participants The result of the capillary test will be retrospectively analyzed and consequently not affect treatment but solely be used for research purposes The results will not be communicated to the study participants
Uppsala biobank In patients already included with written consent in the Uppsala biobank U-CAN follow-up blood samples will be taken according to the biobank routine at inclusion and in case of follow-up httpswwwu-canuuse
End of study Relapse or after one year of inclusion
Data management
The following data will be entered and stored in a pseudonymized database REDCap
At inclusion
patient data age BMI smoking comorbidity performance status
tumor data CA125 other tumour markers histology differention grade tumor stage BRCAHRD status radiology findings
previous treatment data surgical and oncological
At clinical visitsrelapse planned follow-up or unplanned visits
CA125 values
symtoms and signs of relapse including radiology
Date and results of capillary tests
The code for personal identification will be stored in a separate file with password Hence data in the research database cannot be linked to individual patients
Assessment of feasibility
To evaluate feasibility and acceptability of the study a short-form questionnaire with 5-7 questions will be handled to study participants at following occasions
Declining participation
Drop-off from study protocol
End of study A semi-structured interviews will be offered to a strategic sample of participants around 10 with various age medical history after completion of the study in order to identify pitfalls and areas of improvement
Statistics power With approximately 250 women fulfilling these inclusion criteria at Uppsala University Hospital and Norrlands University Hospital yearly and an anticipated inclusion rate of 50 we will reach a study population of 125 women in one year With a drop-out of 25 persons 100 will remain for analysis Around 30 of these women will suffer from relapse during the study period With approximately 10 samples participant we consider 1000 samples sufficient for the pilot study
Analyses The collected capillary dry-cards Ahlström AutoCollect are punched in a semi-automated equipment for punches to be analyzed The laboratory analyses for the plasma protein biomarkers will be carried out at the Affinity Proteomics Facility at SciLifeLab Uppsala using a custom assay provided by Olink Proteomics based on absolute quantification The accuracy sensitivity and specificity of the risk score to detect relapse and the correlation with s-CA125 will be calculated with aid from machine learning An optimal cut-off value for the test score will be approximated in ROC-curves either as an individual increase for example a doubling of lowest risk score or at a group level Time difference between raise in the protein panel score and clinical detection of recurrence will be analyzed
These results will be used for power calculation and decision of sampling intervals for the forthcoming RCT
For patients already included in the Uppsala biobank with written consent venous blood samples will be analysed at follow-up and relapse to be able to validate the results from capillary in venous blood
Further challenges with inclusion reasons for drop-out will be analyzed by short-form questionnaire Qualitative interviews with a selected group of study participants will be carried out to explore patient experience and acceptability and lay the foundation for patient information and communication in the RCT
Clinical significance The hypothesis is that more frequent analysis of a protein panel specific for EOC will lead to earlier detection of relapse earlier treatment and a better prognosis Additionally in the future the vision is that women may choose between different ways of follow-up depending on individual risk factors personal preferences and logistic reasons In the long-term the results of the evaluation of the applicability of home-administered blood sampling from this study can be useful in other patient groups as well
PURPOSE AND AIMS Epithelial ovarian cancer EOC is the deadliest of all gynecologic cancers with 700 incident cases per year in Sweden Even though almost three out of four women with EOC relapse within 2-3 years there is a striking lack of prospective trials on optimized follow-up after EOC treatment The research group have previously identified a plasma marker protein panel with high accuracy for ovarian cancer diagnosis and follow-up The aim with this pilot study is to validate the protein panel for its capacity to detect early relapse in symptom-free patients in a user-friendly non-invasive way ie a home-administered capillary sampling Further the results will be the foundation for a forthcoming national prospective randomized trial RCT - the FOLL-OV trial
SURVEY OF THE FIELDPRELIMINARY RESULTS One of the main purposes with a follow-up program is to find cancer relapse at an early stage and thereby improve the patients chance of successful treatment and prolonged survival Yet there is a striking lack of prospective studies in the field
A recent RCT demonstrated eight months prolonged overall survival when treated with surgery at first relapse compared to chemotherapy alone however the survival benefit was limited to women where complete surgical resection was achieved 3 Hence it has become more important than ever to detect relapse as soon as realistically possible when the tumor burden is limited
As of present the Swedish National Guidelines for EOC recommend follow-up 3-4 timesyear during the first two years after completed treatment The follow-up consists of physical and gynecologic examination transvaginal ultrasound and is many times complemented with the EOC biomarker CA125 but this is optional CA125 is an unspecific marker and not elevated in all types of EOC In a Cochrane review evaluating follow-up strategies of women with EOC only one RCT was included and thus further RCTs are needed to evaluate different types of follow-up strategies using outcomes such as survival quality of life QoL cost and psychological effects Importantly in two recent retrospective studies almost no relapses were detected exclusively on physical examination and the need for regular in-clinic visits were questioned in favor of virtual meetings with a review of symptoms and measurements of tumor marker
Clearly better biomarkers for EOC relapse are needed The research group have recently developed a risk score for detection of EOC based on analysis of 11 plasma proteins When validated in two independent clinical cohorts this assay showed a sensitivity of 083091 and specificity of 088092 for separating EOC and histology benign conditions Further we have demonstrated the possibility to track changes in relation to treatment outcome and relapse using the same risk score Using machine learning four distinct risk score trajectories are defined that indicate that it could be possible to detect relapse events up to 60 days prior to the first clinically recorded event These results were conducted using wet plasma but previous investigations show that dried blood spots work well for proteomics analyses with the intended assay PEA although a re-calibration of the risk-score is needed to accommodate differences between the dry and wet format
This pilot study as part of a larger clinical research project aims to re-calibrate the risk-score and to assess it in a clinical setting using a home-based capillary blood sampling
AIMS OUTCOME
The pilot study will be designed as a prospective cohort study with aim to clarify following questions before planning of a national RCT
Calibrationvalidation of the risk score in capillary blood samples
Accuracy of monthly home-sampling and standard Ca125 for diagnosis of relapse
Evaluate the logistics in home-sampling patients instructions registration communication etc
Evaluate the acceptability of home-sampling by semi-structured interviews of a sample of study participants reasons of drop-out communication aspects pros and cons with repeated sampling
METHOD The pilot study will be designed as a prospective cohort study
Study population
Inclusion criteria
18 years of age
Included in the control program for ovarianfallopianprimary peritoneal cancer at Uppsala University Hospital or at Norrlands University Hospital Sweden
Within 3 years after completed primary treatment for stage III-IV EOC or after treatment for relapse
No evidence of disease normal CA 125 and no tumor detected on radiology or clinical examination
Patients on maintenance therapy PARP-inhibitor bevazicumab can be included
Exlusion Other cancer diagnosis within 2 years except squamous skin cancer or basalioma Non-Swedish speaking Not able to understand instructions
Intervention The participants will follow the standard follow-up program with scheduled visit 3-4 timesyear The follow-up consists of physical and gynecologic examination transvaginal ultrasound and sampling of s-CA125
At inclusion the participants will receive written information and sign informed consent
Capillary test
Study participants will be asked to take a capillary blood sample
at inclusion with assistance from study nurse
at home monthly during one year or until relapse
at suspicion of relapse The capillary sample and sent in to the laboratory in an envelope provided to the study participants The result of the capillary test will be retrospectively analyzed and consequently not affect treatment but solely be used for research purposes The results will not be communicated to the study participants
Uppsala biobank In patients already included with written consent in the Uppsala biobank U-CAN follow-up blood samples will be taken according to the biobank routine at inclusion and in case of follow-up httpswwwu-canuuse
End of study Relapse or after one year of inclusion
Data management
The following data will be entered and stored in a pseudonymized database REDCap
At inclusion
patient data age BMI smoking comorbidity performance status
tumor data CA125 other tumour markers histology differention grade tumor stage BRCAHRD status radiology findings
previous treatment data surgical and oncological
At clinical visitsrelapse planned follow-up or unplanned visits
CA125 values
symtoms and signs of relapse including radiology
Date and results of capillary tests
The code for personal identification will be stored in a separate file with password Hence data in the research database cannot be linked to individual patients
Assessment of feasibility
To evaluate feasibility and acceptability of the study a short-form questionnaire with 5-7 questions will be handled to study participants at following occasions
Declining participation
Drop-off from study protocol
End of study A semi-structured interviews will be offered to a strategic sample of participants around 10 with various age medical history after completion of the study in order to identify pitfalls and areas of improvement
Statistics power With approximately 250 women fulfilling these inclusion criteria at Uppsala University Hospital and Norrlands University Hospital yearly and an anticipated inclusion rate of 50 we will reach a study population of 125 women in one year With a drop-out of 25 persons 100 will remain for analysis Around 30 of these women will suffer from relapse during the study period With approximately 10 samples participant we consider 1000 samples sufficient for the pilot study
Analyses The collected capillary dry-cards Ahlström AutoCollect are punched in a semi-automated equipment for punches to be analyzed The laboratory analyses for the plasma protein biomarkers will be carried out at the Affinity Proteomics Facility at SciLifeLab Uppsala using a custom assay provided by Olink Proteomics based on absolute quantification The accuracy sensitivity and specificity of the risk score to detect relapse and the correlation with s-CA125 will be calculated with aid from machine learning An optimal cut-off value for the test score will be approximated in ROC-curves either as an individual increase for example a doubling of lowest risk score or at a group level Time difference between raise in the protein panel score and clinical detection of recurrence will be analyzed
These results will be used for power calculation and decision of sampling intervals for the forthcoming RCT
For patients already included in the Uppsala biobank with written consent venous blood samples will be analysed at follow-up and relapse to be able to validate the results from capillary in venous blood
Further challenges with inclusion reasons for drop-out will be analyzed by short-form questionnaire Qualitative interviews with a selected group of study participants will be carried out to explore patient experience and acceptability and lay the foundation for patient information and communication in the RCT
Clinical significance The hypothesis is that more frequent analysis of a protein panel specific for EOC will lead to earlier detection of relapse earlier treatment and a better prognosis Additionally in the future the vision is that women may choose between different ways of follow-up depending on individual risk factors personal preferences and logistic reasons In the long-term the results of the evaluation of the applicability of home-administered blood sampling from this study can be useful in other patient groups as well
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None