VALTIVE1

VALTIVE1 is study on the validation of Tie2 as the first tumour vascular response biomarker for VEGF inhibitors.

Background

Tumours require a blood supply to provide them with oxygen and nutrients and to enable spread of cancer through blood vessels to other organs (metastasis). The formation of new blood vessels is known as angiogenesis, which is controlled by a growth factor (like a hormone) called Vascular Endothelial Growth Factor (VEGF). The addition of VEGF inhibitors (VEGFi) to conventional anti-cancer therapy postpones recurrence of the disease.

In ovarian cancer, VEGFi improve the overall outcome from the cancer in patients who have advanced stage and high-risk disease. Yet until now there have not been any biomarkers (tests) that could be used to tell patients and their doctors whether the drugs were working or not. This is important as VEGFi have side effects that are unpleasant for the patient. Additionally, VEGFi treatments are expensive.

Biomarker

The VALTIVE team has discovered the first biomarker that tells us whether a VEGFi is blocking a tumour’s blood supply. The test involves measuring a protein in the blood called Tie2, which can be measured from routine blood tests that patients have when coming to the hospital.

When the amount of Tie2 decreases in the blood, we know that tumour blood vessels are blocked by VEGFi. When the level increases, we know that the blood vessels have escaped the control of VEGFi.

Gathering evidence for NHS test

We have shown that the Tie2 test works in our initial studies in ovarian cancer. With VALTIVE study, we would like to collect more evidence in order to establish a test in the NHS that tells patients and their doctors when VEGFi are working and when they stop working.

We are planning two research projects:

VALTIVE1: the initial trial

In the first part (this trial) we will take blood samples from patients who are receiving a VEGFi called bevacizumab for ovarian cancer. We will not change patients’ management and therefore there is no risk in participating. We will study these results and then use them to design a second trial where we aim to demonstrate conclusively the value of the Tie2 test.

VALTIVE2: the subsequent trial

In the second trial we will test the theory that there is no advantage in continuing bevacizumab in a patient whose Tie2 level does not reduce in response to VEGFi. To prove this, patients whose Tie2 level does not reduce will either stop bevacizumab immediately or continue for the currently used 12 months of the drug.