Role of the ATP7A Transporter in Ovarian Cancer (ATHOC)

January 28, 2024 updated by: David Lukanovic, University Medical Centre Ljubljana

ATP7A Transporter as Biomarker for Predicting Chemoresistance of Serous Ovarian Cancer

Ovarian cancer has the highest mortality rate among all gynecologic cancers, with most patients presenting with advanced stage tumors. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time up to 80 % of others develop chemoresistance, rendering recurrent disease incurable. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The aim of the study is to demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

RATIONALE:

Recent studies suggest that the copper efflux transporters ATP7A plays an important role in platinum resistance. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The literature concludes that new methods are required to detect resistant tumor cells at an early chemotherapy stage and suitably adapt treatment. There is still much uncertainty regarding how the fate of platinum compounds in a cell follows the regulatory copper pathways, especially during transport from the cell. The question is also to what extent these processes are cell-specific, especially because experiments to date regarding the role of ATP7A in resistance to platinum compounds have been conducted on nonserous cell lines (especially of the endometrioid histological type).

AIM OF THE STUDY:

Study will evaluate the ATP7A transporter as an important mediator of chemoresistance to platinum compounds to obtain an additional criterion for the optimal treatment strategy for serous ovarian cancer patients. The focus will primarily be on intrinsic chemoresistance, which determines the initial response to chemotherapy. Research to date has failed to evaluate the influence of ATP7A transporter expression solely on serous ovarian cancer.

The study will demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin. Because the measurement of ATP7A in bodily fluids is unreliable, the plan is to measure ceruloplasmin in the patients' ascites. Ceruloplasmin is the main copper-transporting protein in the blood. It is synthesized in the cell and, according to findings in the literature, it is ATP7A that is responsible for delivering copper to ceruloplasmin. When copper binds to ceruloplasmin, there is no other way for it to cross the plasma membrane than via the ATP7A transporter. By measuring the ceruloplasmin level in the ascites, ATP7A activity or its localization on the plasma membrane could indirectly be measured as well. To confirm the suitable measurement of ceruloplasmin in the ascites, its values in the patients' blood plasma and tissue will be measured.

METHODS:prospective clinical trial It will include 30 high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites. The patients will be presented to the gynecological-oncological consultation team at the Ljubljana Division of Gynecology and Obstetrics. Patients for whom neoadjuvant chemotherapy is recommended will be included in the trial.

STATISTICAL ANALYSES: The normality of numerical variables' distribution will be tested with the Shapiro-Wilk test. Relevant parametric tests (Student's t-test) or nonparametric tests (the two-tailed Mann-Whitney U-test) will be used to compare groups.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Department of Gynecology, Division of Gynecology and Obstetrics, Ljubljana University Medical Center
      • Ljubljana, Slovenia
        • Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana.

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites, for whom neoadjuvant chemotherapy is recommended

Exclusion Criteria:

-

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

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: HGSOC
high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites, for whom neoadjuvant chemotherapy is recommended.
Drug: Carboplatin
Patients will receive neoadjuvant chemotherapy according to ESGO guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
concentration of ceruloplasmin
Time Frame: before the start of neoadjuvant chemotherapy
To measure concentration of ceruloplasmin in blood and ascites
before the start of neoadjuvant chemotherapy
expression of ATP7A
Time Frame: before the start of neoadjuvant chemotherapy
To measure expresion of ATP7A
before the start of neoadjuvant chemotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
concentration of ceruloplasmin after chemotherapy
Time Frame: after neoadjuvant chemotherapy - within 6 months
To measure concentration of ceruloplasmin after three to six chemotherapy cycles
after neoadjuvant chemotherapy - within 6 months
expresion of ATP7A after chemotherapy
Time Frame: after neoadjuvant chemotherapy - within 6 months
To measure expresion of ATP7A after three-six cycles of chemotherapy
after neoadjuvant chemotherapy - within 6 months

Collaborators and Investigators

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

Sponsor

University Medical Centre Ljubljana

Collaborators

University of Ljubljana, Faculty of Medicine, Institute of Pharmacology and Experimental Toxicology

Investigators

  • Study Director: Borut Kobal, MD; PhD, Department of Gynecology, Division of Gynecology and Obstetrics, Ljubljana University Medical Center
  • Study Chair: Katarina Černe, MD, PhD, Institute of Pharmacology and Experimental Toxicology, Medical Faculty, University Ljubljana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

March 17, 2021

Primary Completion (Actual)

May 1, 2023

Study Completion (Actual)

January 1, 2024

Study Registration Dates

First Submitted

May 11, 2021

First Submitted That Met QC Criteria

August 3, 2022

First Posted (Actual)

August 5, 2022

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 28, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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