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

Ovarian Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02687321
• Other study ID #: HE4
• Status: Recruiting
• Start date: April 2016
• Est. completion date: January 2020

Study information

• Verified date: July 2018
• Source: Brno University Hospital
• Contact: Vit Weinberger, M.D., Ph.D.
• Phone: +42053223
• Email: vit.weinberger[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Ovarian Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Czechia	Brno University Hospital	Brno
Czechia	Hospital Ceske Budejovice	Ceske Budejovice
Czechia	Faculty Hospital in Hradec Králové	Hradec Králové
Czechia	Hospital Jihlava	Jihlava
Czechia	Faculty Hospital Pilsen	Pilsen
Czechia	General Hospital Prague	Prague
Czechia	Regional Hospital Pilsen	Zlin
Hungary	University of Derecen	Debrecen
Poland	Swietokrzyskie Cancer Center	Kielce
Poland	Cancer Center, M.Sklodowska-Curie Memorial Institute	Kraków
Poland	Medical University of Lublin	Lublin
Poland	Pomeranian Medical University	Szczecin
Poland	Medical University of Warsaw	Warsaw
Poland	Lower Silesian Cancer Center	Wroclaw
Slovakia	Institute of Oncology, Bratislava	Bratislava
Slovakia	National Institute of Oncology, Bratislava	Bratislava
Slovakia	University Hospital Bratislava	Bratislava
Slovakia	FN Trencín	Trencin
Spain	La Paz University Hospital. Madrid	Madrid
Ukraine	Lviv State Regional Oncological Center	L'viv

Sponsors (2)

Lead Sponsor	Collaborator
Brno University Hospital	University Hospital Pilsen

Countries where clinical trial is conducted

Czechia,  Hungary,  Poland,  Slovakia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum levels of tumor marker CA-125	kU/l	two years after study enrollment
Primary	Serum levels of tumor marker HE4	pmol/l	two years after study enrollment
Secondary	Ovarian cancer recurrence diagnosed by computed tomography scan		two years after study enrollment