The purpose of this current study is to evaluate the efficacy and safety of the 3-day oral aprepitant regimen when administered concomitantly with ondansetron, with or without dexamethasone, in pediatric patients, from 6 months to 17 years of age,…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Complete Response (no vomiting and no use of rescue medication) in the 120
hours following the initiation of emetogenic chemotherapy in Cycle 1 (overall
phase).
Secondary outcome
- Complete Response in the 0 to 24 hours following the initiation of emetogenic
chemotherapy in Cycle 1 (acute phase).
- Complete Response in the 25 to 120 hours following the initiation of
emetogenic chemotherapy in Cycle 1 (delayed phase).
- No Vomiting, regardless of rescue medication use, in the 120 hours following
the initiation of emetogenic chemotherapy in Cycle 1 (overall phase).
- safety and tolerability of the three-day oral aprepitant regimen in patients
from 6 months to 17 years of age who are receiving emetogenic chemotherapy in
Cycle 1.
Background summary
Oral aprepitant (EMEND* ), MK-0869 is a potent and selective substance P
(neurokinin 1 (NK1) - receptor) antagonist that is given in combination with
other antiemetic agents for the prevention of chemotherapy induced nausea and
vomiting (CINV). Aprepitant received marketing approval in adults for the
prevention of acute and delayed nausea and vomiting associated with initial and
repeat courses of highly emetogenic chemotherapy (HEC), including high dose
cisplatin in March 2003; and for the prevention of nausea and vomiting
associated with initial and repeat courses of moderately emetogenic
chemotherapy (MEC) in October 2005. For both HEC and MEC, the currently
approved 3-day dosing regimen in adults for orally administered aprepitant is
125 mg on Day 1 followed by 80 mg on Days 2 and 3, in combination with a
5-hydroxtryptamine (5-HT) type 3 receptor antagonist (5-HT3 antagonist) and
dexamethasone. Aprepitant is not yet approved for use in children.
Nausea and vomiting remains a major problem in a significant number of children
undergoing chemotherapy despite the wide use of 5-HT3 antagonists (i.e.,
ondansetron) with or without corticosteroids for antiemetic prophylaxis. Thus,
there is an ongoing need to clarify the role of new anti-emetic agents, such as
aprepitant, in alleviating CINV in children receiving emetogenic chemotherapy.
A recent Phase III study (PN097) was conducted to evaluate the safety of
aprepitant triple therapy in adolescents, aged 12-17 years, with confirmed
solid malignancies undergoing treatment with emetogenic chemotherapy. In PN097,
the aprepitant triple therapy regimen was found to be generally safe and well
tolerated, with the overall adverse event profile similar to what was
previously reported in adults. The pharmacokinetic data in this study suggest
that the aprepitant dosing regimen approved for CINV prevention in adults
should also be appropriate in adolescent patients. Moreover, the use of
aprepitant triple therapy regimen showed numerically greater response rates
compared to the standard regimen suggesting a treatment difference between the
two study arms, although the study was not powered for efficacy.
A second pediatric study examining the pharmacokinetics, safety and exploratory
efficacy of aprepitant triple therapy in pediatric patients ages birth to 17
years, is ongoing (PN134). Results from PN097, PN134, and PN148 (an ongoing
aprepitant pediatric pharmacokinetic study for post-operative nausea and
vomiting (PONV)) are being evaluated together in order to inform
age-appropriate dose(s) for the aprepitant triple therapy regimen in children.
Study objective
The purpose of this current study is to evaluate the efficacy and safety of the
3-day oral aprepitant regimen when administered concomitantly with ondansetron,
with or without dexamethasone, in pediatric patients, from 6 months to 17 years
of age, receiving emetogenic chemotherapy for a documented malignancy.
Study design
Patients will be stratified into 4 age groups as follows:
• 12 to 17 years.
• 6 years to < 12 years.
• 2 years to <6 years.
• 6 months to <2 years.
This study will evaluate a 3-day regimen of oral aprepitant in combination with
the 5-HT3 antagonist ondansetron. Patients will be randomized into 1 of 2
treatment arms and will receive either the 3-day regimen of oral aprepitant, in
combination with ondansetron, beginning on chemotherapy Day 1, or ondansetron
alone. Intravenous (IV) dexamethasone may be administered as part of the
antiemetic regimen at the discretion of the investigator.
The main focus of this study will be on a single cycle of aprepitant (Cycle
1). Patients will have an opportunity to receive open-label aprepitant in
subsequent cycles (Optional Cycles 2-6), if they elect to participate.
Intervention
GROUP 1
Patients 12 to 17 years of age:
Day 1: aprepitant 125 mg capsule PO + ondansetron
Days 2-3: aprepitant 80 mg capsule PO
Patients 6 months to <12 years of age
Day 1: aprepitant PFS: 3.0 mg/kg (up to 125 mg) + ondansetron
Days 2-3: aprepitant PFS: 2.0 mg/kg (up to 80 mg)
GROUP 2 (Control)
Patients 12 to 17 years of age:
Day 1: matching placebo for aprepitant 125 mg capsule PO + ondansetron
Days 2-3: matching placebo for aprepitant 80 mg capsule PO
Patients 6 months to <12 years of age
Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron
Days 2-3: matching placebo PFS: 2.0 mg/kg (up to 80 mg)
Intravenous dexamethasone may be administered as part of the anti-emetic
regimen at the discretion of the investigator. If dexamethasone is
administered as part of the anti-emetic regimen for patients receiving
aprepitant, dexamethasone should be administered at 50% of the established dose
in children. No dose adjustment will be made for patients allocated to receive
placebo for aprepitant; to maintain blinding, dexamethasone will be prepared in
a blinded manner by an unblinded study pharmacist/designee. This recommendation
may be modified, as needed, based on an ongoing pediatric pharmacokinetic study
examining the interaction of dexamethasone and aprepitant in pediatric
patients.
Study burden and risks
Risks: adverse reactions of aprepitant and ondansetron.
Burdens:
- Physical examination at screening/baseline.
- 3x ECG (cycle 1)
- Laboratory Safety test 3x in cycle 1 and 2x per cycle in de optional cycle
2-6
- 1x Laboratory Safety test at Study Discontinuation
- 3 daily administration of aprepitant or placebo administered concomitantly
with ondansetron
- daily completion of patient diary by the patients or their parent for 6
consecutive days
One Merck Drive 1
P.O. Box 100, Whitehouse Station NJ, 08889-0100
US
One Merck Drive 1
P.O. Box 100, Whitehouse Station NJ, 08889-0100
US
Listed location countries
Age
Inclusion criteria
1. Male or female, 6 months to 17 years of age.
2. Patient is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of emetogenicity for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting.
3. Patient with documented malignancy at either original diagnosis or relapse;
4. Patient is expected to receive ondansetron as part of their antiemetic regimen.
5. Patient aged >10 years has a Karnofsky score >= 60; patient aged <= 10 years has a Lansky Play Performance score >= 60 .
Exclusion criteria
1. Patient is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy.;2. Patient has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting. Patient who is asymptomatic is allowed to participate.;3. Patient has abnormal laboratory values as follows :
a. Bone Marrow Function
- Peripheral absolute neutrophil count (ANC) <1000/mm3
- Platelet count <100,000/ mm3
b. Liver Function
- AST>5.0 x upper limit of normal (ULN) for age
- ALT>5.0 x upper limit of normal (ULN) for age
- Bilirubin > 1.5 x upper limit of normal (ULN) for age
c. Renal function
- A serum creatinine > 1.5 x upper limit of normal (ULN) for age;4. Patient has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen.
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 | EUCTR2011-000651-16-NL |
| CCMO | NL36840.078.11 |
| Other | Nog niet bekend |