Ovarian CancerNCT04770376
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
An observational study of Ovarian Cancer, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.
- How many people
- 150 participants
- Where
- 1 siteItaly
- Study dates
- 12 Oct 2020to Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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)
Who may be able to join
- 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
Who cannot join
- 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 ).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
Bologna, 40138
Claudio Zamagni, MD, 051 2144548 ext. +39, zamagniclaudio.sper@aosp.bo.it
About this study
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
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
- Being tested
- Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.
- Keywords
- ovarian cancer, angiopoietin 1, tunica interna endothelial cell kinase 2, VEGF, bevacizumab
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Before start of chemotherapy
Secondary outcomes (3)
relationship between Ang1 and Tie2 levels
relationship between Ang1 and Tie2 levels at baseline, during chemotherapy administration and at progression of disease.
Measured: 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
Measured: 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
Measured: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start12 Oct 2020
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ospedale SS Giovanni e Paolo, Venezia
- Responsible party
- Principal investigator, Claudio Zamagni MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Investigators
- Claudio Zamagni, MD, Principal investigator, Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770376
- Sponsor's protocol ID
- PANGEA
- Status last verified
- Dec 2022
- First submitted
- 22 Feb 2021
- Last updated
- 29 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26126494Oliver 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.
PubMed 25225422Backen 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.
PubMed 24947924Zhou 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.
PubMed 27351218Jayson 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.
PubMed 30405103Ciccolini 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.
PubMed 25691775Loupakis 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.
PubMed 17470880
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04770376
- Acronym / sponsor ID
- PANGEA
- Conditions
- Ovarian Cancer
- Keywords
- ovarian cancer, angiopoietin 1, tunica interna endothelial cell kinase 2, VEGF, bevacizumab
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Collaborators
- Ospedale SS Giovanni e Paolo, Venezia
- Study start
- 12 Oct 2020 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: patients treated with chemotherapy (I-II line) associated to bevacizumab | – | Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.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. |
| Cohort B: patients treated with chemotherapy (I-II line, not associated to antiangiogenic drugs) | – | Other: Observational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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)
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (1 listed)
- 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 ).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | 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) |
Primary outcome
relationship between Ang1 and Tie2 values and response to treatment with bevacizumab
Time frame: Before start of chemotherapy
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).
relationship between VEGF values and response to treatment with bevacizumab
Time frame: Before start of chemotherapy
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.
3 secondary outcomes
relationship between Ang1 and Tie2 levels
Time frame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
anticipation of diagnosis of progression of disease
Time frame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
VEGF evaluation
Time frame: from baseline (before start of chemotherapy) to 52 weeks from start of chemotherapy or progression of disease
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2022.
- Background: PubMed 26126494Gadducci 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.
- Background: PubMed 25225422Oliver 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.
- Background: PubMed 24947924Backen 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.
- Background: PubMed 27351218Zhou 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.
- Background: PubMed 30405103Jayson 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.
- Background: PubMed 25691775Ciccolini 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.
- Background: PubMed 17470880Loupakis 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudio Zamagni, MD principal investigator
Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ovarian Cancer, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Claudio Zamagni, MD (051 2144548 ext. + 39, zamagniclaudio.sper@aosp.bo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relationship between Ang1 and Tie2 values and response to treatment with bevacizumab (time frame: Before start of chemotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04770376, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2022.