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

NCT04770376 | Unknown DMC

• 1 other identifier: PANGEA
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Keywords

ovarian cancer; angiopoietin 1; tunica interna endothelial cell kinase 2; VEGF; bevacizumab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• relationship between Ang1 and Tie2 levels

  from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease

• anticipation of diagnosis of progression of disease

  from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease

• VEGF evaluation

  from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease

Study Arms (2)

Cohort A: patients treated with chemotherapy (I-II line) associated to bevacizumab

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.

Cohort B: patients treated with chemotherapy (I-II line, not associated to antiangiogenic drugs)

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.

Interventions

Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy. OTHER

Collection of blood samples during blood draws performed before each cycle of chemotherapy as per clinical practice.

Cohort A: patients treated with chemotherapy (I-II line) associated to bevacizumab; Cohort B: patients treated with chemotherapy (I-II line, not associated to antiangiogenic drugs)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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

You may not qualify if:

• 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 ).

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead
• Ospedale SS Giovanni e Paolo, Venezia: collaborator

Study Sites (1)

Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii

Bologna, 40138, Italy

RECRUITING

Related Publications (7)

• 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.

  PMID: 26126494 BACKGROUND

• 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.

  PMID: 25225422 BACKGROUND

• 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.

  PMID: 24947924 BACKGROUND

• 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.

  PMID: 27351218 BACKGROUND

• 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.

  PMID: 30405103 BACKGROUND

• 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.

  PMID: 25691775 BACKGROUND

• 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.

  PMID: 17470880 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and plasma samples

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Claudio Zamagni, MD

  Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudio Zamagni, MD

CONTACT

051 2144548; zamagniclaudio.sper@aosp.bo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Medical Oncologist

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: October 12, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 29, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)