Role of the ATP7A Transporter in Ovarian Cancer

NCT05490407 | Completed

• 1 other identifier: UMCL
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Gynecologic Cancer; Ovarian Cancer; High Grade Serous Carcinoma; Chemotherapy Effect

Keywords

Ovarian cancer; Chemoresistance; Predictive marker; ATP7A

Outcome Measures

Primary Outcomes (2)

• concentration of ceruloplasmin

  To measure concentration of ceruloplasmin in blood and ascites

  before the start of neoadjuvant chemotherapy

• expression of ATP7A

  To measure expresion of ATP7A

  before the start of neoadjuvant chemotherapy

Secondary Outcomes (2)

• concentration of ceruloplasmin after chemotherapy

  after neoadjuvant chemotherapy - within 6 months

• expresion of ATP7A after chemotherapy

  after neoadjuvant chemotherapy - within 6 months

Study Arms (1)

HGSOC

OTHER

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

Drug: Carboplatin

Interventions

Carboplatin DRUG

Patients will receive neoadjuvant chemotherapy according to ESGO guidelines

HGSOC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• University of Ljubljana, Faculty of Medicine, Institute of Pharmacology and Experimental Toxicology: collaborator

Study Sites (2)

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

Ljubljana, 1000, Slovenia

Location

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

Ljubljana, Slovenia

Location

Related Publications (5)

• 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.

  PMID: 32570116 BACKGROUND

• 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.

  PMID: 31046081 BACKGROUND

• 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.

  PMID: 15269138 BACKGROUND

• 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.

  PMID: 14676106 BACKGROUND

• 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

  BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Borut Kobal, MD; PhD

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

  STUDY DIRECTOR

• Katarina Černe, MD, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asist. David Lukanovic, MD

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: August 5, 2022
• Study Start: March 17, 2021
• Primary Completion: May 1, 2023
• Study Completion: January 1, 2024
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

SL (2)