A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Chemotherapy-Induced Nausea and Vomiting

Treatments: Drug: Dexamethasone; Drug: Experimental: fosaprepitant; Drug: Comparator: ondansetron; Drug: Ondansetron; Drug: Experimental: aprepitant

Study type: Interventional

Funder types: Industry

Identifiers

NCT00818259

2009_501 (Other Identifier)

0869-134

Details and patient eligibility

About

This study will determine the appropriate dosing regimen of aprepitant and fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric participants from 0 months to 17 years of age.

Full description

Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous administration; the pharmacological effect of fosaprepitant is attributed to aprepitant. The birth to one year old cohort will be initiated in Parts III and IV upon completion of Part II (Steps A and B) in participants <6 months of age.

Enrollment: 92 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is 0 (at least 37 weeks gestation) to 17 years of age
• Is scheduled to receive moderately to highly nausea-inducing chemotherapy or participant did not tolerate a previous chemotherapy regimen that is planned to be repeated
• Is expected to receive ondansetron
• Female participants who have begun menstruating must have a negative pregnancy test
• Weighs ≥3.0 kg if <6 months of age, ≥6.0 kg if >6 months of age, and ≥7.5 kg if > 2 years of age
• Has a pre-existing venous catheter

Exclusion criteria

• Uses any illicit drugs or abuses alcohol
• Is pregnant or breast feeding
• Has a symptomatic central nervous system (CNS) tumor
• Has an infection or other uncontrolled disease other than cancer
• Has known history of heart QT wave prolongation

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

92 participants in 7 patient groups

Part IA-fosaprepitant 115 mg/aprepitant

Experimental group

Description:

Day 1, fosaprepitant intravenous (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

Treatment:

Drug: Experimental: aprepitant

Drug: Dexamethasone

Drug: Experimental: fosaprepitant

Drug: Ondansetron

Part IB-fosaprepitant 150 mg

Experimental group

Description:

Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

Treatment:

Drug: Dexamethasone

Drug: Experimental: fosaprepitant

Drug: Ondansetron

Part IIA-aprepitant 80 mg equiv.

Experimental group

Description:

Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to \<12 years of age - 47 mg/m\^2; 4 months to \<6 months of age - 2.0 mg/kg; 1 month to \<4 months of age - 1.0 mg/kg; birth to \<1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

Treatment:

Drug: Experimental: aprepitant

Drug: Dexamethasone

Drug: Ondansetron

Part IIB-aprepitant 125 mg equiv.

Experimental group

Description:

Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to \<12 years of age - 74 mg/m\^2; 6 months to \<2 years of age - 1.3 mg/kg; 4 months to \<6 months of age - 3.0 mg/kg; 1 month to \<4 months of age - 1.5 mg/kg; birth to \<1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

Treatment:

Drug: Experimental: aprepitant

Drug: Dexamethasone

Drug: Ondansetron

Part III-ondansetron

Active Comparator group

Description:

Ondansetron administered IV per local standard of care on Days 1, 2, and 3 prior to chemotherapy for participants from birth to \<12 years of age. The use of IV dexamethasone is optional with the exception of the birth to one year old cohort.

Treatment:

Drug: Comparator: ondansetron

Drug: Dexamethasone

Part IV-aprepitant regimen

Experimental group

Description:

Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to \<12 years of age - 3.0 mg/kg; 1 month to \<4 months of age - 1.5 mg/kg; Birth to \<1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to \<12 years of age - 2.0 mg/kg; 1 month to \<4 months of age - 1.0 mg/kg; Birth to \<1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to one year old cohort.

Treatment:

Drug: Experimental: aprepitant

Drug: Dexamethasone

Drug: Ondansetron

Part V-fosaprepitant regimen

Experimental group

Description:

Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to \<12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

Treatment:

Drug: Dexamethasone

Drug: Experimental: fosaprepitant

Drug: Ondansetron