Soluble Vascular Endothelial Growth Factor Receptor 2 as Predictor of Benefit From Bevacizumab Beyond Progression in Metastatic Colorectal Cancer

A growing amount of reports has consistently evidenced that a sustained inhibition of the angiogenesis is an effective therapeutic strategy, able to improve the outcome of metastatic colorectal cancer (mCRC) patients.

In the last decade different biologic agents targeting angiogenesis have been approved for the treatment of mCRC, such as bevacizumab, aflibercept and regorafenib, and, more recently, solid evidences have demonstrated the efficacy of a sustained antiangiogenic approach even beyond the first progression to a bevacizumab-containing regimen. In particular, two phase III randomized trials proved the effectiveness of prosecuting bevacizumab in second-line switching the chemotherapeutic regimen in patients already treated with bevacizumab in first-line. Preliminary experiences evidenced that circulating levels of angiogenesis-related markers are significantly modulated during first-line chemotherapy plus bevacizumab. In particular, a wide variability of plasma soluble Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) levels is observed at the time of disease progression and retrospective data suggest that benefit from the continuation of bevacizumab may be restricted to patients with high levels of soluble VEGFR-2 at the first evidence of disease progression. This study aims at prospectively validating those retrospective data.

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Key information

Conditions

Metastatic Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56126, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Male or female of ≥ 18 years of age
Progressive disease during or after first-line chemotherapy plus bevacizumab, including fluoropyrimidine alone (5-fluorouracil or capecitabine), fluoropyrimidine in combination with oxaliplatin (XELOX or FOLFOX regimen) or irinotecan (FOLFIRI regimen) or with oxaliplatin and irinotecan (FOLFOXIRI regimen);
No more than 3 months from the last administration of bevacizumab and evidence of progressive disease are allowed;
Measurable disease according to RECIST 1.1.
Indication to second-line treatment with a bevacizumab-containing second-line regimen (second-line XELOX, FOLFOX, FOLFIRI and FOLFOXIRI plus bevacizumab are allowed);
Neutrophils 1.5 x 109/L, Platelets 100 x 109/L, Hgb >9 g/dl
Total bilirubin 1.5 time the upper-normal limits (UNL) of the institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase 2.5 x UNL, 5 x UNL in case of liver metastases
Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL
Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24 hr
Will and ability to comply with the protocol
Written informed consent to study procedures.

Exclusion criteria

Patient unable to give consent
Absolute contraindications to the use of bevacizumab.

Treatment and study plan

chemotherapy plus bevacizumab

Drug

Every chemotherapy regimen combined with bevacizumab is allowed

Primary outcomes

Progression Free Survival

Time frame: from treatment start until disease progression, according to RECIST 1.1, or death due to any cause, whichever occurs first, up to 12 months after last patient last visit

Sponsors and collaborators

Lead sponsor

Azienda Ospedaliero, Universitaria Pisana

Other

Registry information

Official study title

A Single-arm Phase II Study of Circulating Soluble Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) as Predictor of Benefit From Bevacizumab (Bev) Beyond Progression in Metastatic Colorectal Cancer (mCRC) - the CIRCUS Study

Acronym: CIRCUS

Important dates

Study start: 2015
Primary completion: 2017
Study completion: 2017
First posted: Dec 8, 2015
Registry last updated: Dec 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed