Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04523116 |
| Other study ID # |
A29832 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 14, 2021 |
| Est. completion date |
June 2023 |
Study information
| Verified date |
October 2021 |
| Source |
University of Manchester |
| Contact |
Margherita Carucci, PhD |
| Phone |
+442920687900 |
| Email |
VALTIVE[@]cardiff.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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). Many drugs have been developed that block
VEGF and, in most tumour types, including ovarian cancer, 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. VEGFi are now widely used in cancer medicine, 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.
The VALTIVE team has discovered the first biomarker that informs doctors 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 going to the
hospital. If the test shows that the amount of Tie2 decreases in the blood, it means that
tumour blood vessels are blocked by VEGFi; if, on the contrary, the level increases, the
blood vessels have escaped the control of VEGFi.
The investigators have shown that the Tie2 test works in their initial studies in ovarian and
bowel cancer. In these studies, the Tie2 blood test was based in the research laboratories.
The investigators now wish to establish the test in the Christie Hospital NHS Biochemistry
laboratory in Manchester so that it can be used in clinical practice rather than just as a
research tool. The investigators wish to measure the relationship between loss of control of
VEGF inhibitors as measured by TIE 2 and other standard ways of measuring loss of control of
the tumour like increases on CT scans. There are several reasons why this test is needed for
patients with ovarian cancer:
- VEGFi are effective during a patient's first or subsequent treatments for advanced
ovarian cancer, but it is not clear which individuals are benefitting from treatment
whilst they are on treatment.
- Patients who have already had one course of VEGFi can be re-treated successfully.
- Patients can avoid needless side effects, if there is a way of demonstrating that the
treatment is of no benefit to them.
- This test will help doctors choose the best drug to control ovarian cancer and how long
to continue treatment. This is very important, since other maintenance therapies are now
available and the optimal duration of VEGFi therapy is well known.
- Around the world many teams are developing new combination treatments including VEGFi.
If these new combinations prove effective, it would be possible to use them as
efficiently as possible, as they will be very expensive and may therefore be less
accessible to patients.
These issues highlight the critical need to establish a test in the NHS that tells patients
and their doctors when VEGFi are working and when they stop working.
In VALTIVE1 study, blood samples will be taken from patients who are receiving a VEGFi called
bevacizumab for ovarian cancer. Patients' management will not change during their
participation to the trial. The analysis of the blood sample will support the hypothesis that
patients whose Tie2 level decreases in response to bevacizumab will have ovarian cancer that
is controlled for much longer than those where the Tie2 level does not decrease. These
results will be used to design a second trial where the investigators will prove conclusively
the value of the Tie2 test.
The purpose of VALTIVE1 is to optimise sample acquisition time points and analytical
algorithms to support the design of VALTIVE2, a randomised discontinuation trial. In
VALTIVE2, Tie2-defined, vascular non-responding patients will be randomly allocated to stop
bevacizumab after 9 weeks, by when a response can be detected, or to continue bevacizumab for
the conventional year of treatment.
Both VALTIVE 1 and VALTIVE2 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.
Description:
VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, which will enrol
176 participants who are 16 years or older and who have FIGO stage IIIc/ IV ovarian cancer on
treatment with first-line platinum-based chemotherapy and bevacizumab. Potential participants
will be identified at their treating hospital.
The definition of vascular response is either (i) stable or reduced concentrations of Tie2
after 6 weeks of treatment or (ii) a confirmed reduction in plasma Tie2 of >10% within 9
weeks of starting treatment.
Patients enrolled into the VALTIVE 1 study will provide blood samples twice before treatment
with bevacizumab and then at the end Cycles 1, 2, and 3, at the end of cytotoxic
chemotherapy, at 3 months, 6 months, 9 months, at the end of treatment, and at disease
progression. The early samples will be used to refine the definition and number of required
samples needed to define a Tie2-vascular response. Samples collected at 3 months, 6 months, 9
months, at the end of treatment, and at disease progression will be used to investigate the
relationship between Tie2-defined vascular progression and RECIST1.1- or clinically-defined
Progression Disease (PD).
While the patients receive single agent maintenance bevacizumab, patients will undergo
RECIST1.1 scanning at 3 months, 6 months, 9 months, end of treatment and at disease
progression, if not before. These scans will also be reported to RECIST 1.1.
Progressive disease will be defined by the date of radiological or clinically identified
progressive disease or death.
