Evaluation of the Predictive Value of Blood Levels of Angiopoietin 1 and Endothelial Internal Tunica Cell Kinase 2 in Patients With Ovarian Cancer Treated With Chemotherapy Associated to Bevacizumab

Study Overview
=================
Brief Summary
-----------------
This is a monocentric prospective observational pilot study of translational research in women with advanced ovarian epithelial cancer. The main purpose of this study is to evaluate the predictive value of response to treatment with bevacizumab of the circulating levels of Ang1, Tie2 and VEGF before start of therapy. Secondary aims of the study are to explore the predictive value of response / resistance to bevacizumab of changes in circulating levels of Ang1 and Tie2 during treatment and at progression of disease, and to explore the possible role of circulating VEGF in the modulation of bioavailability of bevacizumab.

Official Title
-----------------
Prospective Pilot Study for the Evaluation of the Predictive Value of Blood Levels of Angiopoietin 1 (ANG1) and Endothelial Internal Tunica Cell Kinase 2 (TiE2) in Patients With Ovarian Cancer Treated With Chemotherapy Associated to bevAcizumab

Conditions
-----------------
Ovarian Cancer

Intervention / Treatment
-----------------
* Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥ 18 years old Diagnosis of histologically confirmed advanced epithelial ovarian carcinoma Women eligible for treatment with a chemotherapy regimen in combination to bevacizumab (Cohort A) Women eligible for treatment with a chemotherapy regimen not associated to antiangiogenic drugs (Cohort B) Evaluable disease according to RECIST 1.1 criteria Patient informed consent signature prior to any study-specific procedure Exclusion Criteria: History of other malignancy within 5 years prior to study entry (except for cutaneous basal cell carcinoma or adequately treated carcinoma in situ of the cervix ).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A: patients treated with chemotherapy (I-II line) associated to bevacizumab<br>Quantification of biomarkers will be performed on 100 patients treated with bevacizumab through the collection of the following samples at different timepoints: 1 serum sample; 2 CTAD plasma samples; 2 K2EDTA plasma samples. The samples will be collected as follows: before the start of chemotherapy; 3 weeks after start of chemotherapy, before start of treatment with bevacizumab; 9 weeks after start of chemotherapy; 15 weeks after start of chemotherapy; 52 weeks after start of chemotherapy; at progression of disease. | Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.<br>* Collection of blood samples during blood draws performed before each cycle of chemotherapy as per clinical practice.<br>|
| Cohort B: patients treated with chemotherapy (I-II line, not associated to antiangiogenic drugs)<br>Quantification of biomarkers will be performed on 50 patients treated with chemotherapy through the collection of the following samples at different timepoints: 1 serum sample; 2 CTAD plasma samples; 2 K2EDTA plasma samples. The samples will be collected as follows: before the start of chemotherapy; 3 weeks after start of chemotherapy, before start of treatment with bevacizumab; 9 weeks after start of chemotherapy; 15 weeks after start of chemotherapy; 52 weeks after start of chemotherapy; at progression of disease. | Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.<br>* Collection of blood samples during blood draws performed before each cycle of chemotherapy as per clinical practice.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relationship between Ang1 and Tie2 values and response to treatment with bevacizumab | Relationship between baseline values of Ang1 and Tie2 (considered individually or combined with each other) and response to treatment with bevacizumab (according to RECIST 1.1 criteria). | Before start of chemotherapy | 
| relationship between VEGF values and response to treatment with bevacizumab | Relationship between baseline values of endogenous VEGF (plasma CTAD levels) and released by platelets during the clot phase (serum levels) and response to treatment with bevacizumab. | Before start of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relationship between Ang1 and Tie2 levels | relationship between Ang1 and Tie2 levels at baseline, during chemotherapy administration and at progression of disease. | from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease | 
| anticipation of diagnosis of progression of disease | possible anticipation of diagnosis of progression of disease through evaluation of Ang1 and Tie2 | from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease | 
| VEGF evaluation | Evaluation of free VEGF, bevacizumab-bound VEGF and available bevacizumab in relation to clinical response | from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian cancer, angiopoietin 1, tunica interna endothelial cell kinase 2, VEGF, bevacizumab