Study of Microcirculatory Effects of Bevacizumab in Patients Treated for Metastatic Colon Cancer or Glioblastoma

NCT ID: NCT01810744

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2015-05-31

Brief Summary

The treatment of the most common cancers (colon, breast, lung, liver and kidney) has recently added a new therapeutic class known as the "anti-angiogenic". It was born from a better understanding of tumor growth requires the development of neo-vessels. These new vessels are of major importance for the viability of the tumor but also the birth of metastases. This neo-angiogenesis is complex and results from an imbalance between pro-angiogenic factors and anti-angiogenic factors. Growth factor VEGF and its receptors (VEGFR-1, VEGFR-2 and VEGFR-3) are a way of survival of endothelial cells required for tumor neoangiogenesis. The anti-angiogenic drugs currently available on the market are bevacizumab (Avastin ®), sunitinib (Sutent ®) and sorafenib (Nexavar ®). The mechanism of anti-angiogenic action of these three main drugs are pharmacological inhibition of the VEGF pathway.

These new anti-angiogenic therapies, however, have significant adverse effects are common and some other more serious but rare.

Hypertension is the most common side effect observed in patients treated with anti-VEGF. This is usually iatrogenic hypertension controlled by antihypertensive therapy and rarely compromises the pursuit of anti-angiogenic therapy. More rarely, it can have serious consequences malignant hypertension, severe hypertension refractory reversible posterior leukoencephalopathy associated with severe hypertension have also been reported.

The pathophysiology of hypertension may be due to the neutralization of major physiological effects of VEGF in endothelial cell and therefore the vascular wall.

The study of the microcirculation is not only useful in the diagnosis of microvascular but also macrovascular disease in the evaluation of chronic arterial and venous severe it determines the prognosis. In these indications, capillaroscopy remains the gold standard for all work pathophysiological because visualization of phenomena measured avoids artifacts and difficulties of interpretation. It then appealed to additional technology to directly measure the capillary pressure, capillary flow velocity, and indirectly assess capillary permeability and function of lymphatic canaliculi. The simplest of these technological inputs: video microscopy and digital image analysis, have also improved the practice of routine clinical capillaroscopy in its main field of application, evaluation of microangiopathy connective. The examination can be performed more quickly and easily archived and quantified.

Only two studies on 14 and 16 patients were able to see a decrease in capillary density correlated with the therapeutic activity of anti-angiogenic the tumor mass and metastasis.

Thus, we propose to quantify in a number of relatively large patient patients the decrease in capillary density as well as the relationship between the decrease in the number of capillaries and anti-tumor response.

The study will also aim to measure the prevalence of hypertension in patients treated with bevacizumab and to establish the link between these data and the modification of the capillary microcirculation.

Conditions

Metastatic Colorectal Cancer; Glioblastoma; Bevacizumab; Capillaroscopy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

metastatic colorectal cancer

Patients treated by bevacizumab will be follow up by capillaroscopy and blood pressure measurements.

Group Type: OTHER

capillaroscopy

Intervention Type: OTHER

blood pressure measurement

Intervention Type: OTHER

glioblastoma

Patients treated by bevacizumab will be follow up by capillaroscopy and blood pressure measurements.

Group Type: OTHER

capillaroscopy

Intervention Type: OTHER

blood pressure measurement

Intervention Type: OTHER

Interventions

capillaroscopy

Intervention Type: OTHER

blood pressure measurement

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• signed informed Consent
• Medical Examination
• Patients with metastatic colorectal cancer
• Patients with a glioblastoma
• patient to receive treatment with bevacizumab not yet started
• MRI for patients with glioblastoma or scanner TAP for patients carrying a metastatic colon cancer performed within 3 weeks before inclusion.

Exclusion Criteria

• Bevacizumab already initiated or history of antiangiogenic treatment
• Inability legal (persons deprived of liberty or under guardianship)
• Pregnant or lactating women
• Can not sign consent or unable to undergo medical follow up for geographical, social or psychological reasons
• Patients not covered by Medicare including CMU
• Estimated life of over 3 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Georges Francois Leclerc

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François Ghiringhelli, Professor

Role: PRINCIPAL_INVESTIGATOR

Centre Georges Francois Leclerc

Locations

Centre Georges François Leclerc

Dijon, , France

Countries

France

References

Fumet JD, Bertaut A, Bengrine L, Lapierre P, Vincent J, Ghiringhelli F, Falvo N. Capillary density has no value as an early biomarker of bevacizumab efficacy in metastatic colorectal cancers: a prospective clinical trial. Oncotarget. 2017 Dec 1;9(16):12599-12608. doi: 10.18632/oncotarget.22822. eCollection 2018 Feb 27.

Reference Type: DERIVED

PMID: 29560093 (View on PubMed)

Other Identifiers

001-FANI-2012

Identifier Type: -

Identifier Source: org_study_id