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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: chemotherapy plus bevacizumab

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Italy
  • PI
    • Pisa, PI, Italy, 56126
      • Azienda Ospedaliero Universitaria Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with mCRC progressed on or after a 1st-line bevacizumab-containing regimen and candidate to continue bevacizumab beyond progression, in combination with a 2nd-line chemotherapy regimen.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	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

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 3, 2015
• First Posted (Estimate): December 8, 2015

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CIRCUS