Clinical trial NCT04770376: 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
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ovarian Cancer
Keywords: ovarian cancer
angiopoietin 1
tunica interna endothelial cell kinase 2
VEGF
bevacizumab
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
Collaborators: name: Ospedale SS Giovanni e Paolo, Venezia
First posted: 2021-02-25
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A sample size of 100 patients with advanced epithelial ovarian carcer is expected to be enrolled in Cohort A (I-II line of chemotherapy associated to bevacizumab) and 50 patients with advanced epithelial ovarian carcer is expected to be enrolled in Cohort B (I-II line of chemotherapy, not associated to antiangiogenic drugs)

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.


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 ).

Primary outcomes:
measure: relationship between Ang1 and Tie2 values and response to treatment with bevacizumab
timeFrame: Before start of chemotherapy
measure: relationship between VEGF values and response to treatment with bevacizumab
timeFrame: Before start of chemotherapy
Secondary outcomes:
measure: relationship between Ang1 and Tie2 levels
timeFrame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
measure: anticipation of diagnosis of progression of disease
timeFrame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
measure: VEGF evaluation
timeFrame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
Study officials:
affiliation: Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii
name: Claudio Zamagni, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.
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.
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.
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.