NCT01121640

Brief Summary

The Novel Markers Trial will compare the safety, feasibility and effectiveness of two different epithelial ovarian cancer screening strategies that use CA125 and add HE4 as either a first or second line screen. This study is the next step in a larger research effort to develop a blood test that can be used as a screening method for the early detection of epithelial ovarian cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
854

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Nov 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2009

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

May 10, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 12, 2010

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 7, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 7, 2015

Completed
Last Updated

December 13, 2018

Status Verified

December 1, 2018

Enrollment Period

5.5 years

First QC Date

May 10, 2010

Last Update Submit

December 11, 2018

Conditions

Epithelial Ovarian Cancer

Keywords

Ovarian CancerScreeningBiomarkers

Outcome Measures

Primary Outcomes (1)

  • Positive predictive value of each of the two screening protocols

    Calculated as number of women with a significant lesion identified at a protocol-indicated procedure divided by number of women with protocol-indicated surgical procedures performed.

    From first screen through remaining study period

Secondary Outcomes (2)

  • Screening compliance

    From first screen through remaining study period

  • Cancer related distress and health related quality of life

    At baseline, each screen, 6 weeks post-surgery to remove remaining ovary/ies, and 6 months after post-surgical assessment

Study Arms (2)

CA125 every screen, HE4 at confirmatory screen.

OTHER

CA125 will be used at every screen. Women with a parametric empirical Bayes (PEB) longitudinal algorithm score above the 90th percentile will be asked to return for early recall screening. Women with a PEB score above the 95th percentile will be referred for confirmatory measurements of CA125 and HE4. If confirmatory test results are higher than expected, a transvaginal ultrasound will be performed.

Procedure: CA125 assay on Abbott Architect i1000SR platformProcedure: HE4 assay on Architect i1000SR platformProcedure: Transvaginal Ultrasound

CA125 and HE4 at every screen.

OTHER

CA125 and HE4 will both be used at every screen. Women with a PEB score above the 95th percentile on either CA125 or HE4 will be referred for confirmatory measurements of CA125 and HE4. If confirmatory test results are higher than expected, a transvaginal ultrasound will be performed.

Procedure: CA125 assay on Abbott Architect i1000SR platformProcedure: HE4 assay on Architect i1000SR platformProcedure: Transvaginal Ultrasound

Interventions

CA125 assay on Abbott Architect i1000SR platformPROCEDURE

Bead-based sandwich ELISA style assay

Also known as: Abbott Architect CA125 assay
CA125 and HE4 at every screen.CA125 every screen, HE4 at confirmatory screen.
HE4 assay on Architect i1000SR platformPROCEDURE

Bead-based sandwich ELISA style assay

Also known as: Abbott Architect HE4 assay
CA125 and HE4 at every screen.CA125 every screen, HE4 at confirmatory screen.
Transvaginal UltrasoundPROCEDURE

Sonogram will be obtained only if confirmatory markers are elevated. Exam is restricted to ovarian evaluation.

CA125 and HE4 at every screen.CA125 every screen, HE4 at confirmatory screen.

Eligibility Criteria

Age25 Years - 80 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Risk Group 1, Women ages 25 - 80:
  • The subject has tested positive for a deleterious germ line mutation in BRCA1 or BRCA2.
  • Risk Group 2, Women ages 35 - 80, Pedigree conditions can be satisfied by multiple primary cancers in the same person:
  • The subject has a personal history of breast cancer diagnosed before or at age 50.
  • OR the subject has a personal history of bilateral breast cancer
  • OR the subject has one first-degree relative with breast cancer diagnosed before or at age 50.
  • OR the subject has two breast cancers in the first or second degree relatives, same lineage, with at least one breast cancer diagnosed before or at age 50.
  • OR the subject has three or more first or second degree relatives, same lineage, with breast cancer diagnosed at any age.
  • OR The family contains at least one ovarian cancer diagnosed at any age in the first or second degree relatives.
  • OR the subject is of Ashkenazi ancestry and has had breast cancer diagnosed at any age.
  • OR The subject is of Ashkenazi Jewish ethnicity and has one first or second degree relative with breast cancer diagnosed at any age (must be in the same lineage as the Ashkenazi ancestry)
  • OR The subject has a male relative with breast cancer diagnosed at any age
  • OR The subject has a personal history of a positive genetic test result for a deleterious germline mutation in the P53 gene.
  • OR The subject has tested positive for a deleterious germline mutation in one of the DNA mismatch repair (MMR) genes associated with the Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, also known as Lynch Syndrome) The MMR genes include MLH1, MSH2, MSH6 and PMS2.
  • OR the subject has a first or second degree relative with an identified deleterious germline BRCA1 or BRCA2 mutation, but has not yet undergone testing herself.
  • +5 more criteria

You may not qualify if:

  • Removal of both ovaries for any reason.
  • History of ovarian, fallopian tube cancer or peritoneal carcinomatosis.
  • Currently pregnant.
  • Unable or unwilling to provide informed consent.
  • Unwilling to provide the name of a physician.
  • Unwilling to sign informed consent and/or medical records release form.
  • Current untreated malignancy (other than non-melanoma skin cancer).
  • Currently receiving adjuvant chemotherapy or radiation therapy for cancer (except tamoxifen or aromatase inhibitors +/- lupron). Patients who are being treated may enroll 3 months after completion of last treatment.
  • Intraperitoneal surgery within the last 3 months (laparoscopy or laparotomy).
  • A medical condition that would place subject at risk as a result of the blood donation, including but not limited to bleeding disorders, chronic infectious disease, emphysema or serious anemia.
  • Subject has a family member who is a carrier of a BRCA or MMR gene mutation and the subject has undergone genetic testing that included the family mutation and no mutation was found, and there are no cases of ovarian cancer in the family.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (4)

  • Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Drescher CW, Paley P, Urban N. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecol Oncol. 2010 Mar;116(3):378-83. doi: 10.1016/j.ygyno.2009.10.087. Epub 2009 Nov 28.

    PMID: 19945742BACKGROUND

  • Anderson GL, McIntosh M, Wu L, Barnett M, Goodman G, Thorpe JD, Bergan L, Thornquist MD, Scholler N, Kim N, O'Briant K, Drescher C, Urban N. Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst. 2010 Jan 6;102(1):26-38. doi: 10.1093/jnci/djp438. Epub 2009 Dec 30.

    PMID: 20042715BACKGROUND

  • Lowe KA, Andersen MR, Urban N, Paley P, Dresher CW, Goff BA. The temporal stability of the Symptom Index among women at high-risk for ovarian cancer. Gynecol Oncol. 2009 Aug;114(2):225-30. doi: 10.1016/j.ygyno.2009.03.015. Epub 2009 May 7.

    PMID: 19427026BACKGROUND

  • Andersen MR, Karlan BY, Drescher CW, Paley P, Hawley S, Palomares M, Daly MB, Urban N. False-positive screening events and worry influence decisions about surgery among high-risk women. Health Psychol. 2019 Jan;38(1):43-52. doi: 10.1037/hea0000647. Epub 2018 Nov 15.

    PMID: 30431292DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Ovarian EpithelialOvarian Neoplasms

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Study Officials

  • Nicole Urban, ScD

    Fred Hutchinson Cancer Center

    PRINCIPAL INVESTIGATOR

  • Beth Karlan, MD

    Cedars-Sinai Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
SCREENING
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 10, 2010

First Posted

May 12, 2010

Study Start

November 1, 2009

Primary Completion

May 7, 2015

Study Completion

May 7, 2015

Last Updated

December 13, 2018

Record last verified: 2018-12

Locations

US(5)