To investigate the effect of fluid infusion to prevent deterioration of kidney function due to pemetrexed, during treatment with carboplatin, pemetrexed and pembrolizumab in patients with non-squamous NSCLC. The primary objective is to reduce the…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoints are a decline in kidney function (AKD) based on: eGFR < 60
mL.min-1 per 1.73m2 for < 3 months, or decrease in eGFR by > 35 or increase in
serum creatinine >50% for <3 months.
Secondary outcome
TIme to occurence of AKD
Rate of decline kidney function (eGFR)
Treatment dose intensity, including number of dose reductions
Background summary
Platinum-pemetrexed chemotherapy combined with pembrolizumab is standard
first-line treatment for patients with non-squamous non-small cell lung cancer
(NSCLC) without driver mutation (EGFR mutation or ALK translocation) and
programmed death ligand 1 (PD-L1) expression below 50%. Pemetrexed is known to
cause renal failure. Pemetrexed is almost exclusively eliminated by the kidney.
Renal impairment during pemetrexed maintenance therapy may lead to permanent
kidney injury and impair future treating options. Exploring strategies for
protection from development of nephrotoxicity is valuable. We hypothesize that
hydration during treatment with pemetrexed decreases the risk of developing
renal impairment.
Study objective
To investigate the effect of fluid infusion to prevent deterioration of kidney
function due to pemetrexed, during treatment with carboplatin, pemetrexed and
pembrolizumab in patients with non-squamous NSCLC. The primary objective is to
reduce the incidence of acute kidney disease (AKD) from 30 to 10%. Secondary
objective is to prevent the development of chronic kidney disease (CKD).
Study design
This is a randomized controlled multicenter study to investigate the effect of
fluid infusion to prevent deterioration of kidney function due to pemetrexed,
during treatment with carboplatin, pemetrexed and pembrolizumab. Patients will
receive 4 cycles of induction carboplatin (AUC 5), pemetrexed (500mg/m2) and
pembrolizumab <65kg: 100mg, from 65kg: 150mg, followed by 4 cycles of
pemetrexed (500mg/m2) and pembrolizumab (<65kg: 100mg, from 65kg: 150mg) as
maintenance therapy. Pations will be randomized 1:1 to receive carboplatin,
pemetrexed and pembrolizumab as standard of care, or with subsequently infusion
of 500mL intravenous saline 0.9%. Blood samples for measurement of creatinine
in order to estimate renal function, will be drawn at baseline and prior to
start of each treatment cycle, which is standard of care.
Intervention
Intravenous infusion of 500mL NatriumChloride 0.9%
Study burden and risks
The intervention in this study is the infusion of 500mL saline 0.9%,
subsequently after chemo-immunotherapy infusion. The risk of decompensation
cordis due to the extra fluid infusion is small, since patient with cardiac
failure are excluded. The risk of blood withdrawals is negligible and part of
standard of care. The benefit is the hypothesed reduction of the development of
kidney damage.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
Age > 18 years
Patients must be willing and capable of giving written informed consent
Patients with advanced non-squamous cell lung cancer, receiving first line
treatment with pemetrexed/pembrolizumab maintenance after
carboplatin/pemetrexed/pembrolizumab.
ECOG 0-2
Adequate hematological, renal and liver functions.
Exclusion criteria
• Subject with an active auto-immune disease requiring systemic treatment
• Lung disease requiring systemic steroids in doses of >10 mg prednisolone (or
equivalent dose of another steroid)
• Previous allogeneic or organ transplant
• Known heart failure
• Myocardial infarction previous 6 months
• Serious concomitant systemic disorders (for example active infection,
unstable cardiovascular disease) which in the opinion of the investigator would
compromise the patient's ability to complete the study, or would interfere with
the evaluation of the efficacy and safety of the study treatment
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2022-001975-15-NL |
| CCMO | NL77514.078.22 |