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AzTrials

Gynecologic CancerATHOCNCT05490407

Role of the ATP7A Transporter in Ovarian Cancer

A study testing Carboplatin in people with Gynecologic Cancer and Ovarian Cancer, run by University Medical Centre Ljubljana at 2 sites in Slovenia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 80 years, women only
What is being tested?
Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesSlovenia
Study dates
17 Mar 2021to 1 Jan 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • -

Trial locations and contacts

2 sites in 1 country.

Slovenia2 sites

  • Department of Gynecology, Division of Gynecology and Obstetrics, Ljubljana University Medical Center

    Ljubljana, 1000

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

    Ljubljana

Other trials in Slovenia

About this study

Official title: 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.

Read the 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.

Being tested
Carboplatin
Keywords
Ovarian cancer, Chemoresistance, Predictive marker, ATP7A
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Patients will receive neoadjuvant chemotherapy according to ESGO guidelines

Study groups in NCT05490407
Study groupRoleWhat they receive
HGSOCOtherhigh-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites, for whom neoadjuvant chemotherapy is recommended.
Receives: Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. concentration of ceruloplasmin

    To measure concentration of ceruloplasmin in blood and ascites

    Measured: before the start of neoadjuvant chemotherapy

  2. expression of ATP7A

    To measure expresion of ATP7A

    Measured: before the start of neoadjuvant chemotherapy

Secondary outcomes (2)

  1. concentration of ceruloplasmin after chemotherapy

    To measure concentration of ceruloplasmin after three to six chemotherapy cycles

    Measured: after neoadjuvant chemotherapy - within 6 months

  2. expresion of ATP7A after chemotherapy

    To measure expresion of ATP7A after three-six cycles of chemotherapy

    Measured: after neoadjuvant chemotherapy - within 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2022
  2. Study start17 Mar 2021
  3. Primary completion1 May 2023
  4. Study completion1 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05490407
Sponsor's protocol ID
UMCL
Acronym
ATHOC
Status last verified
Jan 2024
First submitted
11 May 2021
Last updated
30 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lukanovic D, Herzog M, Kobal B, Cerne K. The contribution of copper efflux transporters ATP7A and ATP7B to chemoresistance and personalized medicine in ovarian cancer. Biomed Pharmacother. 2020 Sep;129:110401. doi: 10.1016/j.biopha.2020.110401. Epub 2020 Jun 20.

    PubMed 32570116

  • Colombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I, Morice P, Pignata S, Ray-Coquard I, Vergote I, Baert T, Belaroussi I, Dashora A, Olbrecht S, Planchamp F, Querleu D; ESMO-ESGO Ovarian Cancer Consensus Conference Working Group. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent diseasedagger. Ann Oncol. 2019 May 1;30(5):672-705. doi: 10.1093/annonc/mdz062.

    PubMed 31046081

  • Samimi G, Safaei R, Katano K, Holzer AK, Rochdi M, Tomioka M, Goodman M, Howell SB. Increased expression of the copper efflux transporter ATP7A mediates resistance to cisplatin, carboplatin, and oxaliplatin in ovarian cancer cells. Clin Cancer Res. 2004 Jul 15;10(14):4661-9. doi: 10.1158/1078-0432.CCR-04-0137.

    PubMed 15269138

  • Samimi G, Varki NM, Wilczynski S, Safaei R, Alberts DS, Howell SB. Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5853-9.

    PubMed 14676106

  • Lukanović D, Kobal B, Černe K. Ovarian Cancer: Treatment and Resistance to Pharmacotherapy. Reproductive Medicine. 2022; 3(2):127-140. https://doi.org/10.3390/reprodmed3020011

Questions about this trial

What is this clinical trial studying?

A study testing Carboplatin in people with Gynecologic Cancer and Ovarian Cancer, run by University Medical Centre Ljubljana at 2 sites in Slovenia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

concentration of ceruloplasmin (time frame: before the start of neoadjuvant chemotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05490407, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.

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