Tumor Microenvironment in Ovarian Cancer

Ovarian Cancer Stage IV Clinical Trial

— MICO  

Official title:

Study of the Role of the Tumor Microenvironment in Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06272240
• Other study ID #: 17380
• Status: Recruiting
• Start date: January 2, 2024
• Est. completion date: January 2027

Study information

• Verified date: January 2024
• Source: University of Udine
• Contact: Giuseppe Vizzielli, Prof.
• Phone: 3403990822
• Email: giuseppe.vizzielli[@]uniud.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

A detailed understanding of molecular mechanism of cancer genesis is fundamental to develop innovative and personalized therapies. The new frontier in biomedical research is represented by organoids, a three-dimensional cell culture system obtained from a tissue fragment that accurately reproduces the essential properties of the original tissue in vitro, which could provide a valuable model for explanation of ovarian cancers pathogenesis and will allow to predict the response to a specific therapy. With this research project, we expect to generate ovarian cancer organoids to characterize in vitro interactions and molecular pathway among tumor cells, immune cells, and resident microbiota (intratumoral bacteria and/or microbial-derived molecules).

Description:

Background Proved the importance of microenviroment in the onset and progression of ovarian cancer, a detailed understanding of molecular mechanism of cancer genesis is fundamental to develop innovative and personalized therapies.

Primary Objective The new frontier in biomedical research is represented by organoids, a three-dimensional cell culture system obtained from a tissue fragment that accurately reproduces the essential properties of the original tissue in vitro, which could provide a valuable model for explanation of ovarian cancers pathogenesis and will allow to predict the response to a specific therapy.

Study Hypothesis To generate of ovarian cancer organoids to characterize in vitro interactions and molecular pathway among tumor cells, immune cells, and resident microbiota (intratumoral bacteria and/or microbial-derived molecules).

Trial Design Patients with primary diagnosis of epithelial ovarian cancer (EOC) (stage III and IV according to FIGO) referred to the Obstetrics-Gynecology Department of ASUFC for surgical removal will be selected. It is expected that organoids will be cultured from 50 patients over the course of 3 years, obtained by removed tissue from which pathologist will collect a fragment of tumor tissue and one from adjacent normal tissue (as a healthy control). From tumor tissue they will extract three different fragments: one for the identification of cells composing the Tumor Microenvironment (TME) (through single-cell analysis), one for microbiome analysis, and one for organoid generation to be conducted at the laboratories of the Department of Medical Area.

Inclusion/Exclusion Criteria Patients with a diagnosis of EOC will be considered eligible if they meet these criteria: Age: 18 years - 80 years, serous ovarian carcinoma and FIGO Stage III/IV EOC. They will be excluded in case of ongoing or suspended immunosuppressive therapy within the last 6 months, congenital or acquired immunodeficiency, immunosuppressive state, administration of chemotherapy for another neoplasm in the past 12 months, non-epithelial ovarian tumors, patients not undergoing surgical intervention, BMI higher than 30, absence of Informed Consent.

Primary Endpoint With this research project, we expect to understand if it is also possible to stratify ovarian cancer patients based on the activation of AhR in cells of the Tumor Microenvironment (TME), including tumor cells and immune cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2027
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age > 18 years

• Age < 80 years

• Serous ovarian carcinoma

• FIGO Stage III-IV

Exclusion Criteria:

• Ongoing or suspended immunosuppressive therapy within the last 6 months

• Congenital or acquired immunodeficiency

• Immunosuppressive state

• Administration of chemotherapy for another neoplasm in the past 12 months

• Non-epithelial ovarian tumors

• Patients not undergoing surgical intervention

• BMI > 30

• Absence of Informed Consent

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer Stage III
• Ovarian Cancer Stage IV
• Ovarian Neoplasms

Intervention

Other:
• Ovarian Cancer Organoids
To characterize in vitro interactions and molecular pathway among tumor cells, immune cells, and resident microbiota (intratumoral bacteria and/or microbial-derived molecules)

Locations

Country	Name	City	State
Italy	Università degli Studi di Udine	Udine	UD

Sponsors (1)

Lead Sponsor	Collaborator
University of Udine

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Banerjee S, Tian T, Wei Z, Shih N, Feldman MD, Alwine JC, Coukos G, Robertson ES. The ovarian cancer oncobiome. Oncotarget. 2017 May 30;8(22):36225-36245. doi: 10.18632/oncotarget.16717. — View Citation

Hezaveh K, Shinde RS, Klotgen A, Halaby MJ, Lamorte S, Ciudad MT, Quevedo R, Neufeld L, Liu ZQ, Jin R, Grunwald BT, Foerster EG, Chaharlangi D, Guo M, Makhijani P, Zhang X, Pugh TJ, Pinto DM, Co IL, McGuigan AP, Jang GH, Khokha R, Ohashi PS, O'Kane GM, Gallinger S, Navarre WW, Maughan H, Philpott DJ, Brooks DG, McGaha TL. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity. Immunity. 2022 Feb 8;55(2):324-340.e8. doi: 10.1016/j.immuni.2022.01.006. — View Citation

Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter-Maskowitz A, Weiser R, Mallel G, Gigi E, Meltser A, Douglas GM, Kamer I, Gopalakrishnan V, Dadosh T, Levin-Zaidman S, Avnet S, Atlan T, Cooper ZA, Arora R, Cogdill AP, Khan MAW, Ologun G, Bussi Y, Weinberger A, Lotan-Pompan M, Golani O, Perry G, Rokah M, Bahar-Shany K, Rozeman EA, Blank CU, Ronai A, Shaoul R, Amit A, Dorfman T, Kremer R, Cohen ZR, Harnof S, Siegal T, Yehuda-Shnaidman E, Gal-Yam EN, Shapira H, Baldini N, Langille MGI, Ben-Nun A, Kaufman B, Nissan A, Golan T, Dadiani M, Levanon K, Bar J, Yust-Katz S, Barshack I, Peeper DS, Raz DJ, Segal E, Wargo JA, Sandbank J, Shental N, Straussman R. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. 2020 May 29;368(6494):973-980. doi: 10.1126/science.aay9189. — View Citation

Ranhotra HS, Flannigan KL, Brave M, Mukherjee S, Lukin DJ, Hirota SA, Mani S. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity. Nucl Receptor Res. 2016;3:101199. doi: 10.11131/2016/101199. — View Citation

Ricci F, Bizzaro F, Cesca M, Guffanti F, Ganzinelli M, Decio A, Ghilardi C, Perego P, Fruscio R, Buda A, Milani R, Ostano P, Chiorino G, Bani MR, Damia G, Giavazzi R. Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic alterations. Cancer Res. 2014 Dec 1;74(23):6980-90. doi: 10.1158/0008-5472.CAN-14-0274. Epub 2014 Oct 10. — View Citation

Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985. — View Citation

Yang J, Huang S, Cheng S, Jin Y, Zhang N, Wang Y. Application of Ovarian Cancer Organoids in Precision Medicine: Key Challenges and Current Opportunities. Front Cell Dev Biol. 2021 Aug 2;9:701429. doi: 10.3389/fcell.2021.701429. eCollection 2021. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	• Composition of the tumor microenvironment (including the immune system and intratumoral microbiota). • Generate organoids	Characterize the composition of the tumor microenvironment (including the immune system and intratumoral microbiota). Generate organoids from cells derived from ovarian tissue.	from enrollment to the end of follow up at 36 months