VASCular Impact of Angiogenic Treatment in Patients With Advanced Colorectal Cancer

NCT04813913 | Completed Phase 4

• 1 other identifier: 2017/0184 HP
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Antiangiogenic treatments are used in many tumor locations such as metastatic colorectal cancer (mCRC) with a significant improvement in carcinological results on overall survival and / or progression-free survival. However, their use is characterized by an increase in side effects and in particular cardiovascular effects such as high blood pressure (hypertension). One of the main classes of antiangiogens used in this indication is that of monoclonal antibodies, the leader of which is bevacizumab (Avastin®, Roche, Bale, Switzerland). Bevacizumab works by inhibiting endothelial vascular growth factor-dependent neoangiogenesis (vascular endothelial growth factor VEGF). In the reference studies, the inhibition of VEGF, whether extracellular (monoclonal antibody directed against VEGFA) or intracellular (receptor inhibitors with tyrosine kinase activity), induces hypertension of all grades, observed in 25% to 40 % of patients including 8 to 17% of severe grades (≥ grade 3 NCI-CTCAE). In terms of pathophysiology, inhibition of VEGFA results in a decrease in the availability of nitric oxide (NO) at the endothelial level and the appearance of arteriolar rarefaction. This induces an increase in peripheral resistance responsible ultimately for an increase in blood pressure. The occurrence of hypertension induced by anti-VEGF treatment seems to be predictive of the carcinological response in certain oncological situations such as metastatic breast cancer9, glioblastoma and mRCC. Furthermore, it has also been shown that there is an early attack on the elastic conductance arteries (branches of the aorta and its main ones) characterized by an increase in their rigidity in patients exposed to a VEGF receptor inhibitor with tyrosine activity. kinase or bevacizumab. This increase, whose poor prognostic impact is known at the cardiovascular level is largely independent of the rise in blood pressure and reflects a direct toxicity of treatments at the level of the artery wall. This increase in rigidity, refused when the pressure rises, would be predictive of a low carcinological response rate at 6 months. However, these data are based on populations that are heterogeneous in terms of carcinology and the position prior to or concomitant with other antineoplastic treatments. In this context, the evaluation of arterial stiffness in the same patient population would make it possible to better define the involvement of the conductive arteries in a clearly defined clinical situation. Joint measurements of the plasma concentration of the treatment as well as those of factors derived from the endothelium and circulating tumor markers which, to our knowledge, have never been carried out in these patients, would make it possible to better specify the mechanisms of involvement and the links between exposure, arterial toxicity and carcinologic efficacy of bevacizumab. Of course, in order to assess more precisely the inherent impact of chemotherapy on the conductance arteries, the evolution of arterial stiffness must take into account the possible effects in patients receiving, for essentially clinical and biological reasons, systemic treatment without antiangiogenic.

Conditions

Oncology

Outcome Measures

Primary Outcomes (1)

• Difference in carotid stiffness between baseline and at 4 months of bevacizumab treatment.

  Difference in carotid stiffness estimated by the delta of the pulse wave velocity calculated by an applanation tonometry and an ultrasound at the level of the common carotid artery, between baseline and at 4 months of bevacizumab treatment.

  Through study completion, an average of 4 months

Secondary Outcomes (7)

• Difference of central arterial pressures between baseline and at 4 months of bevacizumab treatment

  Through study completion, an average of 4 months

• Difference of central arterial pressures between baseline and at 1 month of bevacizumab treatment

  1 month

• Difference of peripheral arterial pressures between baseline and at 4 months of bevacizumab treatment

  4 months

• Difference of peripheral arterial pressures between baseline and at 1 month of bevacizumab treatment

  1 month

• The evolution of circulating concentrations of markers of endothelial function (nitric oxide [NO], epoxyeicosatrienoic acids [EETs], sVE-cadherin),

  1 and 4 months

Study Arms (1)

bevacizumab

EXPERIMENTAL

bevacizumab in combination with IV fluoropyrimidine chemotherapy.

Drug: Bevacizumab in combination with chemotherapy based on fluoropyrimidine IV

Interventions

Bevacizumab in combination with chemotherapy based on fluoropyrimidine IV DRUG

Enrollement of major patient with colorectal cancer of the adenocarcinoma type, stage IV, histologically confirmed, naive in antineoplastic treatment and eligible to start a systemic carcinological treatment comprising bevacizumab in combination with chemotherapy based on fluoropyrimidine IV. The main objective is to show that there is an increase in the stiffness of the carotid artery at 4 months in patients with stage IV colorectal cancer exposed to bevacizumab.

bevacizumab

Eligibility Criteria

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

You may qualify if:

• Patient at least 18 years old,
• Patient with colorectal cancer of the adenocarcinoma type, stage IV, histologically confirmed, mutated or wild tumor RAS status (exons 2, 3 and 4 of the KRAS and NRAS genes), mutated or wild BRAF status, naive in antineoplastic treatment
• Patient eligible to start systemic carcinological treatment including bevacizumab in combination with chemotherapy based on IV fluoropyrimidine,
• General condition WHO grade less than or equal to 3,
• Life expectancy greater than 4 months,
• Patient who has read and understood the information letter and signed the consent form,
• Patient affiliated to a social security scheme,

You may not qualify if:

• Previous exposure to anti-VEGF,
• Other histologically proven neoplasia not considered in complete remission or considered in complete remission for less than two years,
• Bilateral carotid breath,
• Absence of peripheral pulse of the two upper limbs,
• Contraindication to AVASTIN 25 mg / ml concentrate for solution for infusion:
• Hypersensitivity to the active substance or to any of the excipients,
• Hypersensitivity to Chinese hamster ovarian cell products or other human or humanized recombinant antibodies,
• Patients:
• Unhealed ulcer or wound,
• having uncontrolled pre-existing hypertension (PAS\> or = 170 mm Hg after three repeated measurements at rest),
• having a history of arterial thromboembolism (transient ischemic attack (TIA), cardiovascular accident (stroke) or recent (\<6 months) and / or symptomatic myocardial infarction (MI)
• with known proteinuria\> 2g / 24h or in whom proteinuria\> 2g / 24h is discovered in the case of a positive urine strip 3+ for proteins (excluding urinary tract infection),
• on aspirin\> 325 mg / d,
• with a colonic prosthesis in place,
• Systemic treatment with anti-EGFR monoclonal antibodies,

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

CHU de ROUEN

Rouen, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: March 24, 2021
• Study Start: May 5, 2019
• Primary Completion: July 21, 2022
• Study Completion: July 21, 2022
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

FR (1)