Clinical trial NCT01810744: Study of Microcirculatory Effects of Bevacizumab in Patients Treated for Metastatic Colon Cancer or Glioblastoma
Official title: Study of Microcirculatory Effects of Bevacizumab in Patients Treated for Metastatic Colon Cancer or Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Colorectal Cancer
Glioblastoma
Bevacizumab
Capillaroscopy
Lead sponsor: Centre Georges Francois Leclerc
Sponsor class: OTHER
First posted: 2013-03-13
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: change in the density of capillaries
timeFrame: baseline and after 15 days of bevacizumab treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre Georges François Leclerc
Study officials:
affiliation: Centre Georges Francois Leclerc
name: François Ghiringhelli, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.