Clinical trial NCT01121640: A Trial Using Novel Markers to Predict Malignancy in Elevated-Risk Women
Official title: A Randomized Controlled Trial Using Novel Markers to Predict Malignancy in Elevated-Risk Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epithelial Ovarian Cancer
Keywords: Ovarian Cancer
Screening
Biomarkers
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: The Marsha Rivkin Center for Ovarian Cancer Research
name: Canary Foundation
name: Swedish Medical Center
name: City of Hope Medical Center
name: Cedars-Sinai Medical Center
name: Stanford University
name: Fox Chase Cancer Center
First posted: 2010-05-12
Enrollment: 854
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

Detailed description: Epithelial ovarian cancer (EOC) is usually lethal unless it is diagnosed at an early stage, thus early detection is likely to play an important role in reducing its mortality. Within the Ovarian Specialized Programs of Research Excellence Pacific Ovarian Cancer Research Consortium (POCRC) researchers have been working for a decade to discover, develop, and validate biomarkers (proteins or substances found in blood) that could help save lives by detecting EOC early. During the last five years several biomarkers, including CA125, have been evaluated for their ability to detect EOC at an earlier stage. The best markers will now be studied in a new randomized controlled trial of ovarian cancer screening.

Eligibility criteria: Inclusion Criteria:

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.
* OR the subject has a first or second degree relative with an identified deleterious germline MMR gene mutation, but has not yet undergone testing herself.
* OR Probability of carrying a BRCA1 or BRCA2 mutation given family pedigree of breast and ovarian cancers exceeds 20% by any existing BRCA mutational probability model.

Risk Group 3, Women ages 45 - 80:

* Have measurement of CA125, HE4, MMP7 or Mesothelin exceeding the 95th percentile;
* OR have a relative risk of at least 2 based on the EpiRisk logistic regression model including age, family history, and other risk factors.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Positive predictive value of each of the two screening protocols
timeFrame: From first screen through remaining study period
Secondary outcomes:
measure: Screening compliance
timeFrame: From first screen through remaining study period
measure: Cancer related distress and health related quality of life
timeFrame: At baseline, each screen, 6 weeks post-surgery to remove remaining ovary/ies, and 6 months after post-surgical assessment
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Nicole Urban, ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center
name: Beth Karlan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.