To prospectively study the effect of salt restriction on the rise in blood pressure in response to anti-cancer treatment with the VEGF inhibitor sunitinib and regorafenib.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean difference in blood pressure rise between the treatment cycle with and the
treatment cycle without salt restriction.
Secondary outcome
Effects of salt restriction on rise in endothelin-1, proteinuria as marker for
nephropathy and pharmacokinetics of sunitinib and regorafenib; if an effect on
blood pressure is shown, further analyses of effects on renal transporter
proteins will be performed to explain the mechanism of salt sensitivity.
Background summary
Growth and metastatic spread of a malignant tumor requires the formation of new
blood vessels. Recent therapies target this mechanism by inhibiting vascular
endothelial growth factor (VEGF)-signalling. Although this is an effective
anticancer treatment, many patients develop cardiovascular side effects such as
hypertension and kidney disease, frequently requiring dose reduction and/or
early termination of treatment while still effective. Therefore, strategies to
prevent VEGF inhibitor-induced toxicity are urgently needed.
In animal studies, VEGF inhibitor-induced hypertension is salt-sensitive. In
this study, we want to study salt restriction in cancer patients treated with
VEGF inhibitors sunitinib and regorafenib as a strategy to attenuate or prevent
VEGF inhibitor-induced toxicity, primarily the rise in blood pressure.
Study objective
To prospectively study the effect of salt restriction on the rise in blood
pressure in response to anti-cancer treatment with the VEGF inhibitor sunitinib
and regorafenib.
Study design
This is a single centre prospective open-label intervention study to compare a
treatment cycle of sunitinib or regorafenib using salt restriction with the
previous treatment cycle without salt restriction
Intervention
A salt restricted diet (<4 grams/day) will be started during the off-treatment
period under guidance of a specialized dietititan. Salt-less bread will be
provided.
Study burden and risks
The main purpose is to study efficacy of the intervention and thereby give
important pathophysiological insights in VEGF inhibitor-induced toxicity.
Patients will undergo a salt restricted diet for a maximum of 5 weeks, which
can be challenging. Earlier studies in patients with kidney disease showed that
this intervention is acceptable for this short period and the risk of
undernutrition is negligible. The patient federation *Leven met blaas- of
nierkanker* previously agreed that this is an acceptable burden especially
since, if effective, patients might benefit themselves immediately. Further
burden comes from repeated 24h ABPM, extra blood sampling and urine collection.
Dr Molewaterplein 40
Rotterdam 3015 CD
NL
Dr Molewaterplein 40
Rotterdam 3015 CD
NL
Listed location countries
Age
Inclusion criteria
• Registered indication for sunitinib or regorafenib in the standard treatment regime 4 weeks treatment and 2 weeks off (sunitinib) or 3 weeks on/1 week off (regorafenib).
• Blood pressure well controlled at baseline (<135/85 mmHg at 24h ABPM or <140/90 mmHg office)
• Written informant consent
• Age >= 18 years,
Exclusion criteria
• Not providing informed consent or not capable of giving informed consent
• Using antihypertensive drugs other than a calcium channel blocker at baseline
• Weight loss of 10% or more in the previous six months indicating undernutrition
• Insufficient understanding of Dutch language
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66666.078.18 |