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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04770376
• Other study ID #: PANGEA
• Status: Recruiting
• Start date: October 12, 2020
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Contact: Claudio Zamagni, MD
• Phone: 051 2144548
• Email: zamagniclaudio.sper[@]aosp.bo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 ).

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Other:
• Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.
Collection of blood samples during blood draws performed before each cycle of chemotherapy as per clinical practice.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii	Bologna

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna	Ospedale SS Giovanni e Paolo, Venezia

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Backen A, Renehan AG, Clamp AR, Berzuini C, Zhou C, Oza A, Bannoo S, Scherer SJ, Banks RE, Dive C, Jayson GC. The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer. Clin Cancer Res. 2014 Sep 1;20(17):4549-4558. doi: 10.1158/1078-0432.CCR-13-3248. Epub 2014 Jun 19. — View Citation

Ciccolini J, Serdjebi C, Barbolosi D, Lacarelle B, Barlesi F. Ang1 and Tie2 are predictive biomarkers for bevacizumab-letter. Clin Cancer Res. 2015 Feb 15;21(4):934. doi: 10.1158/1078-0432.CCR-14-2832. No abstract available. — View Citation

Gadducci A, Lanfredini N, Sergiampietri C. Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research. Crit Rev Oncol Hematol. 2015 Oct;96(1):113-28. doi: 10.1016/j.critrevonc.2015.05.009. Epub 2015 Jun 16. — View Citation

Jayson GC, Zhou C, Backen A, Horsley L, Marti-Marti K, Shaw D, Mescallado N, Clamp A, Saunders MP, Valle JW, Mullamitha S, Braun M, Hasan J, McEntee D, Simpson K, Little RA, Watson Y, Cheung S, Roberts C, Ashcroft L, Manoharan P, Scherer SJ, Del Puerto O, Jackson A, O'Connor JPB, Parker GJM, Dive C. Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer. Nat Commun. 2018 Nov 7;9(1):4672. doi: 10.1038/s41467-018-07174-1. — View Citation

Loupakis F, Falcone A, Masi G, Fioravanti A, Kerbel RS, Del Tacca M, Bocci G. Vascular endothelial growth factor levels in immunodepleted plasma of cancer patients as a possible pharmacodynamic marker for bevacizumab activity. J Clin Oncol. 2007 May 1;25(13):1816-8. doi: 10.1200/JCO.2006.10.3051. No abstract available. — View Citation

Oliver KE, McGuire WP. Ovarian cancer and antiangiogenic therapy: caveat emptor. J Clin Oncol. 2014 Oct 20;32(30):3353-6. doi: 10.1200/JCO.2014.57.4574. Epub 2014 Sep 15. No abstract available. — View Citation

Zhou C, Clamp A, Backen A, Berzuini C, Renehan A, Banks RE, Kaplan R, Scherer SJ, Kristensen GB, Pujade-Lauraine E, Dive C, Jayson GC. Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab. Br J Cancer. 2016 Jul 12;115(2):228-35. doi: 10.1038/bjc.2016.194. Epub 2016 Jun 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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