Development of a Biomarker to Predict the Efficacy of Anti-angiogenic Therapy in Ovarian Cancer (OutCoME)

Epithelial ovarian cancer (EOC) is a highly angiogenic tumor and drug targeting of angiogenesis is effective in some selected groups of EOC patients. However, no biomarkers are available to predict the effectiveness of this expensive therapy.Investigators believe that Multimerin-2, an extracellular matrix molecule, could serve as a biomarker that can address this clinical need. Multimerin-2 is deposited throughout the vasculature and its expression in EOC-associated vessels is frequently lost, in part due to increased degradation. Multimerin-2 sequesters VEGFA and other angiogenic factors and their release upon degradation of Multimerin-2 could underlie resistance to anti-angiogenic therapy. Indeed, fragments of degradation of Multimerin-2 are found in high concentrations in sera of EOC patients. Furthermore, the loss of Multimerin-2 impairs the function of the vessels, and this could negatively affect the delivery of the drug and the efficacy of the treatment.

With the aim of predicting the efficiency of anti-angiogenic therapy, researchers will evaluate the angiogenic properties and expression of Multimerin-2 in EOC tumors, and develop a new Multimerin-2-based biomarker detectable by liquid biopsy, in order to manage EOC patients in a targeted manner based on the biological characteristics of their tumor.

Study Overview

• Status: Recruiting
• Conditions: Epithelial Ovarian Cancer
• Intervention / Treatment: Other: liquid biopsy

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: Maurizio Maurizio; Phone Number: +390434659516; Email: mmongiat@cro.it

Study Locations

• Italy
  • Aviano, Italy
    • Recruiting
    • Centro di Riferimento Oncologico (CRO), IRCCS
    • Contact: Maurizio Mongiat; Email: mmongiat@cro.it
    • Principal Investigator: Milena Nicoloso
    • Principal Investigator: Maurizio Mongiat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women with histological diagnosis of epithelial ovarian carcinoma (EOC),consecutively referred to the IRCCS CRO of Aviano in the study period

Description

Inclusion Criteria:

1. Female patients aged ≥18 years
2. Histological diagnosis of epithelial carcinoma of the ovary or fallopian tubes or primary carcinoma of the peritoneum, including mixed Mullerian tumours.
3. Stage IIIb, IIIc or IV
4. Performance Status 0-2 according to ECOG
5. Availability of tumor tissue samples and biological fluids for molecular analyses
6. Informed consent for the collection, storage and use of biological material for the CRO Biobank (as specified in the consent of the CRO Biobank, Rev 2 of 03/10/2016), signed and obtained before surgery for suspected EOC.

Exclusion Criteria:

1. Ovarian tumors of low malignant potential (i.e. borderline tumors)
2. Other malignacies within the last 5 years except carcinoma in situ of the cervix or early stage squamous cell or basal cell carcinoma of the skin, as long as they are adequately treated.
3. Active infection or uncontrolled chronic inflammatory disease

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multimerin-2 levels and progression free survival	To investigate whether Multimerin-2 level measured in serum could represent a potential prognostic biomarker (measured as progression free survival) in bevacizumab-treated subjects	from EOC diagnosis diagnosis until first documented progression or death from any cause, up to 2 years
Multimerin-2 levels and progression free survival	To investigate whether Multimerin-2 level measured in urine could represent a potential prognostic biomarker (measured as progression free survival) in bevacizumab-treated subjects	from EOC diagnosis diagnosis until first documented progression or death from any cause, up to 2 years
Multimerin-2 levels and progression free survival	To investigate whether Multimerin-2 level measured in ascites could represent a potential prognostic biomarker (measured as progression free survival) in bevacizumab-treated subjects	from EOC diagnosis diagnosis until first documented progression or death from any cause, up to 2 years

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano
• Investigators: Principal Investigator: Maurizio Maurizio, Centro di Riferimento Oncologico (CRO), IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: CRO2019.053

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