This study has been transitioned to CTIS with ID 2024-517846-32-00 check the CTIS register for the current data. To evaluate the effect of prolonged duration of (fos)aprepitant prophylaxis on the prevention of delayed CINV (complete remission in the…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients who achieve complete response (no vomiting, no retching
and no use of rescue medication) during the 24-72 hours after the final dose of
chemotherapy (delayed phase).
Secondary outcome
Proportion of patients who:
- achieved complete response during the course of chemotherapy until 24h af-ter
the final dose of chemotherapy (acute phase)
- achieved complete response during both the acute and delayed phase (overall
phase)
Time from initiation of emetogenic chemotherapy to:
o the first vomiting episode
o the first rescue medication use
Safety of prolonged use of (fos)aprepitant (AEs considered related by the
investiga-tors)
Pharmacokinetic (PK) parameters (i.e. clearance and volume of distribution) and
in-fluencing PK co-variates as chemotherapeutics
Improvement of CINV complaints according to the Pediatric Nausea Assessment
tool (PeNAT) for children aged 4-<=18 years
Cost-effectiveness of prolonged (fos)aprepitant dosing regimen
Background summary
Prophylaxis of chemotherapy induced nausea and vomiting (CINV) is still a major
problem in children receiving moderate and highly emetogenic therapy. Compared
to adults, children achieve almost 30% less control of CINV using a similar
antiemetic regimen. Courses of chemotherapy in children often last longer than
the approved 3-day (fos)aprepitant regimen. This will be the first randomized
placebo controlled study addressing the question if prolonged duration of
(fos)aprepitant treatment leads to better control of chemotherapy induced
nausea and vomiting in children compared with the standard regimen.
Study objective
This study has been transitioned to CTIS with ID 2024-517846-32-00 check the CTIS register for the current data.
To evaluate the effect of prolonged duration of (fos)aprepitant prophylaxis on
the prevention of delayed CINV (complete remission in the 24-72 hours after the
final dose of chemotherapy) in children. The current 3-day regimen is compared
to a regimen of (fos)aprepitant prophylaxis during the complete course of
chemotherapy in the same patient in subsequent similar courses of chemotherapy,
creating an intrapatient comparison of anti-emetic control.
See protocol section 2 objectives for het secondary objectives.
Study design
a double-blind placebo-controlled randomized cross-over phase III study
Intervention
A randomized comparison of standard of care 3-days (fos)aprepitant followed by
placebo (treatment regimen A) and (fos)aprepitant prophylaxis during the
complete course of chemotherapy (treatment regimen B). Before starting the next
course of similar chemotherapy patients will crossover to the second treatment
regimen (A to B and B to A).
Study burden and risks
The topic of this study on improving the current protocol of anti-emetic
prophylaxis will appeal children and we expect a great willingness to cooperate
with this project. We hypothesize that an increase in duration of aprepitant
prophylaxis from 3 days to the total duration of the course of chemotherapy
will lead to a decreased number of patients experiencing nausea and vomiting.
However, patients could experience side effects of longer (fos)aprepitant
prophylaxes. Although considered rare, we will monitor this carefully.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
these are the eligibility criteria:
- Age must be >= 6 months to <= 18 years at time of study entry and weight >=6kg
- a documented malignancy.
- Patients need to receive moderate or highly emetogenic chemotherapy blocks,
or chemotherapy not previously tolerated due to vomiting, for a minimum
duration of 4 days.
- Chemotherapy schedules need to contain two similar courses of chemotherapy,
which do not necessarily have to be consecutive courses.
- No symptomatic primary or metastatic CNS malignancy causing nausea or
vomiting.
- Patients do not receive scheduled blocks of chemotherapy containing
dexamethasone as part of anti-tumour treatment during the study period.
- Patients aged 16 and greater than 16y with a Karnofsky score of 60 or more or
patients aged 15y or less with a Lansky Play performance score of 60 or more.
- Patient must have a life expectancy of 3 months or more.
- Patients must not use antiemetic treatment within 48h before treatment (see
appendix B).
- Patients must not receive radiation therapy to the abdomen or pelvis in the
week before treatment.
- Patient must not use benzodiazepines or opioids initiated within 48h before
treatment, except for single doses of triazolam, temazepam, or midazolam.
- Continuation of chronic benzodiazepine or opioid therapy is permitted
provided it was initiated >=48 hours prior to study drug administration.
o In patients on chronic warfarin, acenocoumarol, tolbutamide or phenytoin
(metabolised by CYP2C9) therapy should be monitored closely during treatment
with (fos)aprepitant and for 14 days following each course of (fos)aprepitant.
o No use of CYP3A4 substrates/inhibitors within 7 days, or no CYP3A4 inducers
within 30 days of treatment (see appendix B).
- serum creatinine must be <= 1.5 x institutional upper limit of normal (ULN)
according to age.
- AST and ALT must be <= 5 x institutional ULN.
- total bilirubin must be <= 1.5 x institutional ULN
- no history of QT prolongation
- Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed prior to enrollment.
-Female patients with infants must agree not to breastfeed their infants while
on this study.
-Male and female patients of child-bearing potential must agree to use a highly
effective method of contraception approved by the investigator during the
study, following the CTFG recommendations.
-Patients have no history of prior grade 3/4 allergic reaction to any of the
study drugs.
-Patients have no underlying gastrointestinal disease that may interfere with
the absorption of the medication.
Exclusion criteria
see eligibility criteria D4a.
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 |
|---|---|
| EU-CTR | CTIS2024-517846-32-00 |
| EudraCT | EUCTR2021-003311-26-NL |
| CCMO | NL77839.041.21 |