Phenotypic Spectrum of CTCs in Tumors of the Female Reproductive System

Study Overview
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Brief Summary
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The study evaluates the level and molecular profiles of different CTC populations as markers for predicting the risk of developing hematogenous metastases and the effectiveness of treatment in patients with tumors of the female reproductive system (breast cancer, endometrial cancer, and ovarian cancer). The primary objective are: To assess the presence and number of different populations of CTCs at different time points (before biopsy, before surgery, and after surgery). To assess the relationships of different CTCs populations prior to treatment initiation with the effects of neoadjuvant chemotherapy and the risks of recurrence and metastases. To assess the molecular profiles of different CTCs populations in the blood and in ascitic fluid. The secondary objective is to compare the multicolor flow cytometry results with data of ultrasound, CT and/or MRI, serum tumor markers, and immunohistochemical studies in patients with breast cancer, endometrial cancer and ovarian cancer

Detailed Description
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The overall goal is to study the diagnostic and prognostic efficacy of various CTC populations as liquid biopsy markers in tumors of the female reproductive system (breast cancer, endometrial cancer, and ovarian cancer). Phase I study: Determination of different populations of CTCs in blood and ascitic fluid (if any) prior to treatment. The main objectives of the study: To assess the presence and number of different CTC populations at different time points (before biopsy and before surgery) using multicolor flow cytometry. To assess the relationships between different CTCs populations prior to treatment initiation with the effects of neoadjuvant chemotherapy and the risks of recurrence and metastases. To assess the molecular profiles of different CTCs populations in the blood and in ascitic fluid. Additional research tasks: To compare the multicolor flow cytometry results with the data of ultrasound, CT and/or MRI, serum tumor markers, and immunohistochemical studies in patients with breast cancer, endometrial cancer, and ovarian cancer Methodology: Open-label, exploratory, single centre study. Blood and ascitic fluid collected from subjects (if available)

Official Title
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Phenotypic Spectrum of Circulating Tumor Cell Populations as Markers of Liquid Biopsy in Tumors of the Female Reproductive System

Conditions
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Breast Cancer, Ovarian Cancer, Endometrial Cancer

Intervention / Treatment
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* Other: Taking 5 ml of venous blood at different time intervals
* Other: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy if any


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is > 18 years of age A negative pregnancy test (serum beta-human chorionic gonadotropin, beta-HCG) at screening for all patients of childbearing potential. Clinical and radiological diagnosis of breast cancer or Ovarian cancer or Endometrial Cancer General satisfactory condition (according to the ECOG scale ≤2) Subject is capable to undergo the diagnostic investigations to be performed in the study Informed consent Exclusion Criteria: Active current autoimmune disease or history of autoimmune disease Active infection or history of severe infection within the previous 3 months (if clinically relevant at screening) Known HIV positive or chronically active hepatitis B or C The subject has multiple primary malignant tumors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast cancer<br>At least eighty five subjects with breast cancer | Other: Taking 5 ml of venous blood at different time intervals<br> <br> * Other names: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy;Other: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy if any<br> <br> |
| Ovarian cancer<br>At least 32 subjects with ovarian cancer | Other: Taking 5 ml of venous blood at different time intervals<br> <br> * Other names: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy;Other: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy if any<br> <br> |
| Endometrial Cancer<br>At least 33 subjects with endometrial cancer | Other: Taking 5 ml of venous blood at different time intervals<br> <br> * Other names: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy;Other: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy if any<br> <br> |
| Healthy control<br>30 healthy volunteers | Other: Taking 5 ml of venous blood at different time intervals<br> <br> * Other names: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy;|
| Suspected malignant tumor non-verified<br>Patients with suspected malignant tumor, which was not verified by biopsy. Nubmber of patients to be defined | Other: Taking 5 ml of venous blood at different time intervals<br> <br> * Other names: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy;Other: Taking 5 ml EDTA-stabilized ascitic fluid sampled during laparoscopy if any<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTC phenotype | Different populations of CTCs are evaluated by multicolor flow cytometry and may include: СTC, ascitic tumor cells with stemness features without EMT features; CTC, ascitic tumor cells without stemness and EMT features; CTC, ascitic tumor cells without stemness features and with EMT features; CTC, ascitic tumor cells with stemness features and EMT features; Atypical/hybrid cells without stemness features; Atypical cells. | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, endometrial Cancer, ovarian cancer, CTC heterogeneity, cancer stem cells, epithelial-mesenchymal transition, multicolor flow cytometry, liquid biopsy, circulating tumor cell