EMBER: Evaluation of Multiple Protein and Molecular Biomarkers to Estimate Risk of Cancer in Gynecology Patients Presenting With a Pelvic Mass.

Sponsor
Angle plc (Industry)
Overall Status
Completed
CT.gov ID
NCT02781272
Collaborator
University of Rochester (Other)
200
1
71.9
2.8

Study Details

Study Description

Brief Summary

ANGLE has developed the Parsortix™ Cell Separation System (Parsortix), an automated system capable of harvesting rare circulating cells for analysis from a sample of peripheral blood based on cellular size and deformability. In a small pilot study, scientists at the Medical University of Vienna demonstrated that measurement of a combination of mRNA markers extracted from CTCs captured using the Parsortix system could be used to identify women with ovarian cancer. This study is designed to provide specimens for optimization of an assay using clinical and biomarker information (i.e. demographics, imaging results and/or serum tumor markers) in combination with mRNA extracted from rare cells in the blood of women presenting with a pelvic mass for the detection of malignancy.

Primary Objective: Optimization of an assay/algorithm for the differentiation of women with benign pelvic masses from those with malignant pelvic masses using clinical and biomarker information (i.e. demographics, imaging results and/or serum tumor markers) in combination with mRNA markers extracted from rare cells isolated from whole blood. Multiple serum protein markers and mRNA markers will be measured, and the results will be compared to the actual clinical diagnosis made for each subject through other recognized methods (i.e. histopathology). Statistical modeling will be used to combine the clinical information, serum protein markers and/or mRNA markers for estimation of the risk of malignancy. If successful, the resulting risk algorithm will be evaluated in future, appropriately powered, prospective studies.

Exploratory Objective: Use statistical modeling to determine the need for and/or preliminary design of a mathematical algorithm to combine the clinical information, serum protein markers and/or mRNA markers for estimation of the risk of malignancy.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Pelvic imaging
  • Procedure: Blood draw
  • Procedure: Imaging guided biopsy, surgical biopsy or surgical excision

Detailed Description

This study is exploratory in nature and is designed to be hypothesis generating to support the design of future studies. Women diagnosed with a pelvic mass (ovarian, uterine, retroperitoneal, etc.) who are scheduled for an imaging guided biopsy, surgical biopsy or surgical excision for evaluation of their pelvic mass. It is estimated that approximately 200 women will be enrolled for evaluation of the primary and exploratory endpoints. Enrollment into the study will continue beyond 200 women if necessary to obtain a minimum of 50 evaluable women with a histopathologically confirmed malignancy, including ovarian, fallopian, peritoneal, endometrial, cervical, etc.

Within 60 days prior to the pelvic mass evaluation procedure, each subject must have a pelvic imaging study (e.g. ultrasound, CT scan, MRI, etc.) conducted and read to visualize the pelvic mass according to the current standard of care. Results of the pelvic imaging study(ies) will be recorded.

Within 30 days prior to, or on the day of the pelvic mass evaluation procedure, collect up to 35mL of whole blood into one 5mL SST tube, which must be drawn first, followed by three separate 10mL EDTA tubes. Serum from SST tube will be used for protein biomarker testing. Blood from EDTA tubes will be pooled and processed on the Parsortix™ System to capture and harvest rare cells. The captured rare cells will be eluted (harvested) and lysed, and total RNA will be extracted from the cell lysate for evaluation of multiple gene targets.

Imaging guided biopsy, surgical biopsy or surgical excision for evaluation of the pelvic mass will be performed by a qualified individual. Tissue samples will be sent to the local pathology department for histological examination in accordance with standard institutional practices. Results of the histopathological evaluation will be recorded, including the final diagnosis along with histological sub-type, and if available, stage, of cancer where disease is identified. Where possible, representative fresh frozen tissue samples from the pelvic mass will be obtained for research purposes for evaluation of the same mRNA gene targets used in the cell harvests.

Subjects will be considered negative for malignancy:
  • if the subject undergoes surgery and no mass is identified, or;

  • if the histopathological findings are negative for malignancy (i.e. benign conditions).

Subjects will be considered positive for malignancy:
  • if the histological examination of the tissue taken at the time of the biopsy or surgery confirms the presence of a malignancy (i.e. ovarian, primary peritoneal, fallopian tube, endometrial, uterine, cervical, metastatic cancers, etc.).

For the purposes of enrollment, subjects diagnosed with low malignant potential (LMP) / borderline tumors will be considered as benign (negative for malignancy). However, two separate analyses of the final study data will be conducted: one where subjects diagnosed with low malignant potential (LMP) / borderline tumors are classified as being negative for malignancy and a second time where these subjects are classified as being positive for malignancy.

For subjects diagnosed with a malignancy, a bi-annual medical record review will be performed for up to 5 years after their enrollment into the study to collect information regarding their treatment response, chemotherapy sensitivity and resistance, time to recurrence, time to progression and overall survival.

An algorithm for the prediction of benign vs. malignant disease will be constructed using the clinical information, serum biomarkers and mRNA markers. Additional analyses may be performed within and between various histopathological diagnosis sub-groups. The variable selection and algorithm construction will be done using various statistical methods, such as logistic regression, hierarchal clustering, classification and regression trees (CART), ROC curve evaluation, sensitivity/specificity analysis, visual plotting for determination of thresholds, etc. The inputs for evaluation may include continuous variables (e.g. age, ovary and dominant mass dimensions, serum biomarker results, mRNA expression levels, etc.), categorical variables (e.g. age groups, biomarker results by ranges, mRNA expression levels by ranges, etc.), and/or binary variables (e.g. presence or absence of particular risk factors and/or imaging features, age above or below a particular threshold, menopausal status, biomarker results above or below a particular threshold, mRNA expression levels above or below a particular threshold, etc.). A threshold for the resulting algorithm(s) output to differentiate between benign and malignant disease (or a subgroup thereof, such as epithelial ovarian cancer patients only) will be selected to optimize the sensitivity at a set specificity (e.g. maximize sensitivity at a minimum specificity level of >80%).

Upon completion of the long-term follow-up period, the association of the clinical data and markers with the subject's treatment response, chemotherapy sensitivity and resistance, time to recurrence, time to progression and overall survival will be assessed using the appropriate statistical methods (e.g. 2x2 tables, correlation analyses, Cox hazards regression, Kaplan-Meier plotting, etc.).

Study Design

Study Type:
Observational
Actual Enrollment :
200 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
ANG-003 EMBER Study: Evaluation of Multiple Protein and Molecular Biomarkers to Estimate Risk of Cancer in Gynecology Patients Presenting With a Pelvic Mass.
Actual Study Start Date :
Jun 30, 2016
Actual Primary Completion Date :
Jun 1, 2017
Actual Study Completion Date :
Jun 27, 2022

Arms and Interventions

Arm Intervention/Treatment
Women with a pelvic mass

Women diagnosed with a pelvic mass (ovarian, uterine, retroperitoneal, etc.) who are scheduled for an imaging guided biopsy, surgical biopsy or surgical excision for evaluation of their pelvic mass. Must have a pelvic imaging study performed within 60 days prior to surgery and a research blood draw within 30 days prior to surgery.

Procedure: Pelvic imaging
Within 60 days prior to the pelvic mass evaluation procedure, each subject must have a pelvic imaging study (e.g. ultrasound, CT scan, MRI, etc.) conducted and read to visualize the pelvic mass according to the current standard of care. Results of the pelvic imaging study(ies) will be recorded.
Other Names:
  • pelvic ultrasound
  • CT scan
  • MRI scan
  • Procedure: Blood draw
    Within 30 days prior to, or on the day of the pelvic mass evaluation procedure, collect up to 35mL of whole blood into one 5mL SST tube, which must be drawn first, followed by three separate 10mL EDTA tubes.
    Other Names:
  • phlebotomy
  • Procedure: Imaging guided biopsy, surgical biopsy or surgical excision
    Imaging guided biopsy, surgical biopsy or surgical excision for evaluation of the pelvic mass will be performed by a qualified individual. Tissue samples will be sent to the local pathology department for histological examination in accordance with standard institutional practices. Results of the histopathological evaluation will be recorded, including the final diagnosis along with histological sub-type, and if available, stage and grade of cancer where disease is identified.

    Outcome Measures

    Primary Outcome Measures

    1. Histopathological diagnosis [Within 30 days after biopsy or surgical procedure to evaluate pelvic mass]

      Tissue samples taken from the pelvic mass will be evaluated in the URMC GYN pathology department according to institutional guidelines. Results from the histopathological evaluation, including the final diagnosis (i.e. benign, malignant, etc.), histopathology description, and, if malignant, clinical or surgical staging and tumor subtype, will be recorded.

    2. Presence or absence of circulating tumor cells [Up to 30 days prior to biopsy or surgical procedure to evaluate pelvic mass]

      Blood from EDTA tubes will be pooled and processed on the Parsortix™ System to capture and harvest rare cells. The captured rare cells will be eluted (harvested) and lysed, and total RNA will be extracted from the cell lysate for evaluation of multiple gene targets.

    3. Serum protein markers [Up to 30 days prior to biopsy or surgical procedure to evaluate pelvic mass]

      Serum from SST tube will be used for protein biomarker testing.

    Other Outcome Measures

    1. Treatment response [Up to 5 years after enrollment]

      For subjects diagnosed with a malignancy, a bi-annual medical record review will be performed for up to 5 years after their enrollment into the study to collect information regarding their treatment response, chemotherapy sensitivity and resistance, time to recurrence, time to progression and overall survival.

    2. Disease recurrence or progression [Up to 5 years after enrollment]

      For subjects diagnosed with a malignancy, a bi-annual medical record review will be performed for up to 5 years after their enrollment into the study to collect information regarding their treatment response, chemotherapy sensitivity and resistance, time to recurrence, time to progression and overall survival.

    3. Overall survival [Up to 5 years after enrollment]

      For subjects diagnosed with a malignancy, a bi-annual medical record review will be performed for up to 5 years after their enrollment into the study to collect information regarding their treatment response, chemotherapy sensitivity and resistance, time to recurrence, time to progression and overall survival.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Women >18 years of age;

    • Documented evidence of a pelvic mass by imaging;

    • Selected to undergo biopsy, laparotomy or laparoscopy for pathologic evaluation of their pelvic mass;

    • Willing and able to provide written informed consent.

    Exclusion Criteria:
    • Known pregnancy;

    • Previous malignancy within the past 5 years, excluding skin cancers (squamous cell or basal cell);

    • Unwilling or unable to follow protocol requirements or to provide informed consent.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Rochester Medical Center Wilmot Cancer Institute Rochester New York United States 14642

    Sponsors and Collaborators

    • Angle plc
    • University of Rochester

    Investigators

    • Principal Investigator: Richard G Moore, MD, University of Rochester

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Angle plc
    ClinicalTrials.gov Identifier:
    NCT02781272
    Other Study ID Numbers:
    • ANG-003
    First Posted:
    May 24, 2016
    Last Update Posted:
    Jun 28, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Angle plc
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 28, 2022