The Role of HE4 in the Follow-up of Advanced Ovarian, Fallopian Tube and Primary Peritoneal Cancer

July 24, 2018 updated by: Vit Weinberger, Brno University Hospital

The Role of HE4 in the Follow-up of Advanced Ovarian, Fallopian Tube and Primary Peritoneal Cancer: First Prospective Multicentre Observational Study

To evaluate and to compare the effectiveness of CA-125 and HE4 serum levels in epithelial ovarian cancer (OC) in follow-up in terms of time to detection of elevation after the end of the first line treatment. To evaluate the lead-time of the rise of marker levels before epithelial OC recurrence diagnosis by Computed tomography (CT) imaging method. To evaluate the appropriate HE4 cut-off value for follow-up of patients after the treatment of ovarian, Fallopian tube and primary peritoneal cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Ovarian cancer (OC) is the second most common gynaecologic cancer and the leading cause of death from gynaecologic malignancy among women in industrialized countries. The global incidence in both developed and developing countries can be estimated as 165,000 new cases per year. A heavy difference in prognosis exists between the early-stage disease FIGO I-II (International Federation of Gynaecology and Obstetrics and the advanced stages (FIGO III-IV). Unfortunately, at present, we do not have an effective screening strategy for this malignancy; most (70-80%) of the cases are diagnosed as advanced-stage disease, and this explains the high mortality rate. These aggressive features of the OC encouraged in recent years a big effort in order to find new strategies for early diagnosis of OC. These studies focused dominant on new markers and diagnostic algorithms among new markers. HE4 is one of the most promising. It is a protein initially identified in the epithelium of the distal epididymis and may be involved in sperm maturation. Despite its wide distribution, it is overexpressed only in pathological tissue, and it has demonstrated good sensitivity and specificity in detecting OC, overcoming the traditional role of CA-125. Despite an aggressive upfront treatment strategy (surgery plus chemotherapy), leading to clinical remission in more than 80% of patients, the relapse-free survival varies from 95.8% (for early FIGO stages) to 33.6% (for advanced stages) at 2 years. At present, periodical evaluation of CA-125 combined with physical examination is the recommended strategy for OC follow-up, typically every 3 to 4 months in the first 2 years after primary treatment and then every 6 months until the fifth year. Five years' overall survival rate, however, is 49.7% (ranging from 83%-89% in stage I OC to 18% in stage IV). New markers should be tested in the follow-up of patients with OC to improve the surveillance program performance: the challenge is to try to anticipate the diagnosis of OC recurrence and to translate this early diagnosis of relapse in a survival improvement. Few studies only are available to date about HE4 use in follow up of ovarian cancer. All of these studies analyzed a small number of women (8-73). HE4 was shown as an earlier indicator of recurrence of OC with respect to CA-125, with a lead-time of 5 to 8 months. Only 1 prospective controlled study has been published. In this study the sensitivity and specificity of HE4, alone or in association with other markers (CA-125, CA-72-4), seems to be higher in the diagnosis of the OC relapse with respect to CA-125 alone. The other side of the question is whether the patient is advantaged by an earlier detection of the recurrent disease, in terms of overall survival, disease-free survival, and quality of life. Early detection and treatment of cancer in general or its recurrence are usually associated with better outcomes for patient, this being the rationale behind screening programs and follow-up strategies. In OC follow-up, periodical CA-125 evaluation can detect recurrence of cancer about 5 months before clinical signs or symptoms. At the same time, we have to remind, that treatments of relapsing OC are rarely curative and have heavy adverse effects, and elevation of CA-125 is often cause of anxiety in patients undergoing follow-up. The main study, that tried to clarify the role of CA-125 in OC follow-up was MRC OV05/EORTC (European Organisation for Research and Treatment of Cancer) 55955 trial a randomized study comparing early versus delayed treatment in women with relapsed OC. Patients in the delayed treatment group were treated only at clinical or symptomatic relapse. Women assigned to early treatment started chemotherapy 4.8 months earlier than those allocated to the delayed treatment. With a median follow-up of 56.9 months, there was no evidence of a difference in overall survival between the 2 groups. In particular, the results provided no evidence of an improved overall survival or a better quality of life in the early treatment group. The authors' explanation for these findings was that the lead-time between CA-125 rise and the clinical recurrence could be too short for chemotherapy to give a beneficial effect. At present, periodical evaluation of CA-125 combined with physical examination is the recommended strategy for OC follow-up, typically every 3 to 4 months in the first 2 years after primary treatment and then every 6 months until the fifth year. Five years' overall survival rate, however, is 49.7% (ranging from 83%-89% in stage I OC to 18% in stage IV).

Study Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Brno, Czechia, 62500
      • Ceske Budejovice, Czechia, 544256
        • Recruiting
        • Hospital Ceské Budejovice
        • Contact:
          • Petr Valha, M.D.
      • Hradec Králové, Czechia
        • Recruiting
        • Faculty Hospital in Hradec Králové
        • Contact:
          • Iva Sedlakova, MD, Ph.D.
      • Jihlava, Czechia
        • Recruiting
        • Hospital Jihlava
        • Contact:
          • Petra Herboltova, MD
      • Pilsen, Czechia, 30100
        • Recruiting
        • Faculty Hospital Pilsen
        • Contact:
          • jiri Presl, M.D., Ph.D.
      • Prague, Czechia, 12000
        • Recruiting
        • General Hospital Prague
        • Contact:
          • Filip Frühauf, M.D.
      • Zlin, Czechia, 585068
        • Recruiting
        • Regional Hospital Pilsen
        • Contact:
          • Pavel Havelka, M.D., Ph.D.
  • Hungary
      • Debrecen, Hungary
        • Recruiting
        • University of Derecen
        • Contact:
          • Robert Poka, Prof.
  • Poland
      • Kielce, Poland, 25734
        • Recruiting
        • Swietokrzyskie Cancer Center
        • Contact:
          • Kamil Zalewski, M.D., Ph.D.
      • Kraków, Poland
        • Recruiting
        • Cancer Center, M.Sklodowska-Curie Memorial Institute
        • Contact:
          • Pavel Blecharz, Prof.
      • Lublin, Poland, 20093
        • Recruiting
        • Medical University of Lublin
        • Contact:
          • Krysztow Kulak, M.D.
      • Szczecin, Poland
        • Recruiting
        • Pomeranian Medical University
        • Contact:
          • Aleksandra Strojna, MD
      • Warsaw, Poland, 02091
        • Recruiting
        • Medical University of Warsaw
        • Contact:
          • Nadil Abdalla, M.D.
      • Wroclaw, Poland, 58413
        • Recruiting
        • Lower Silesian Cancer Center
        • Contact:
          • Marcin Jedryka, M.D., Ph.D.
  • Slovakia
      • Bratislava, Slovakia, 81250
        • Recruiting
        • Institute of Oncology, Bratislava
        • Contact:
          • Ladislav Masak, M.D., Ph.D.
      • Bratislava, Slovakia, 83310
        • Recruiting
        • National Institute of Oncology, Bratislava
        • Contact:
          • Tibor Lengyel, M.D.
      • Bratislava, Slovakia
        • Recruiting
        • University Hospital Bratislava
        • Contact:
          • Mikulas Redecha, MD, Ph.D.
      • Trencin, Slovakia, 505820
        • Recruiting
        • FN Trencin
        • Contact:
          • Peter Kascak, M.D., Ph.D.
  • Spain
      • Madrid, Spain, 28046
        • Recruiting
        • La Paz University Hospital. Madrid
        • Contact:
          • Ignacio Zapardiel, M.D., Ph.D.
  • Ukraine
      • L'viv, Ukraine
        • Recruiting
        • Lviv State Regional Oncological Center
        • Contact:
          • Oleh Tsolko, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Patient with histologically confirmed advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma with complete remission after first line treatment.

Description

Inclusion Criteria:

  • advanced ovarian cancer, stage FIGO III and IV
  • histology types: high-grade serous, low-grade serous, endometrioid, clear cell, undifferentiated
  • completed ovarian cancer surgery and platinum-based chemotherapy

Exclusion Criteria:

  • positivity of tumor markers CA 125 and HE4 during study enrollment
  • signs of cancer at computed tomography scan during study enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Advanced ovarian cancer patients
Patient with histologically confirmed advanced (FIGO III and IV) epithelial ovarian, fallopian tube or primary peritoneal carcinoma with complete remission after first line treatment are included into the study. The patient is regularly followed up every 3-4 months, blood sample collection is performed to determinate tumor marker found in blood, elevated by the presence of cancer recurrence. In case of one or both of tumor markers are elevated, computed tomography examination with intravenous contrast agent of chest and abdomen is performed to detect the recurrence of the disease.
Other: Determination of CA 125 and HE4, Computed tomography
Blood sample collection to determinate tumor marker found in blood elevated by the presence of cancer recurrence.In case of one or both of tumor markers are elevated, computed tomography examination with intravenous contrast agent of chest and abdomen is performed to detect the recurrence of the disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum levels of tumor marker CA-125
Time Frame: two years after study enrollment
kU/l
two years after study enrollment
Serum levels of tumor marker HE4
Time Frame: two years after study enrollment
pmol/l
two years after study enrollment

Secondary Outcome Measures

Outcome Measure
Time Frame
Ovarian cancer recurrence diagnosed by computed tomography scan
Time Frame: two years after study enrollment
two years after study enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brno University Hospital

Collaborators

University Hospital Pilsen

Investigators

  • Principal Investigator: Vit Weinberger, M.D., Ph.D., University Hospital Brno
  • Principal Investigator: Jiri Presl, M.D., Ph.D., University Hospital Pilsen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Anticipated)

January 1, 2020

Study Completion (Anticipated)

January 1, 2020

Study Registration Dates

First Submitted

February 17, 2016

First Submitted That Met QC Criteria

February 19, 2016

First Posted (Estimate)

February 22, 2016

Study Record Updates

Last Update Posted (Actual)

July 26, 2018

Last Update Submitted That Met QC Criteria

July 24, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HE4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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