Fosaprepitant PK/PD CINV in Pediatric Cancer Patients

Phase 1

• Conditions: Chemotherapy-induced nausea and vomiting (CINV) associated with emetogenic chemotherapy; MedDRA version: 19.0Level: LLTClassification code 10036899Term: Prophylaxis against chemotherapy induced vomitingSystem Organ Class: 100000004865; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002340-24-EE
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09-21
• Last Update Posted: 9 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 227

Inclusion Criteria

For Cyc 1: Criteria specific to patients 12-17 yrs old are only applicable to the partially-blinded portion of the study. The open-label portion of the study will not recruit patients 12-17yrs.
1. Patient is 0 (at least 37 weeks gestation) to less than 12 yrs at time of study entry (randomization).
2. Parent/guardian (legally auth. repr.) agrees to the patient’s participation as indicated by parent/legal guardian signature on the informed consent form (ICF). Patient 12-17 yrs old, or as required by local regulation, assents and has the ability to understand the nature and intent of the study including the ability to comply with study procedures, complete study diary, and is willing to keep scheduled study visits. The parent/guardian or patient may also provide consent/assent for Future Biomedical Research (FBR). However, the patient may participate in the main trial without participating in the FBR.
3. Patient is scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting.
4. Patient is expected to receive ondansetron as part of their antiemetic regimen.
5. Female patient who has begun menses has a negative urine pregnancy test prior to Treatment Day 1 of each Study Cycle. A female patient who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 28 days prior to, throughout, and for at least one month following the last dose of study medication. Women taking oral contraception must agree to add a barrier form of contraception. For countries where abstinence is not considered an acceptable method of birth control, a locally acceptable birth control method must be used.
6. Patient >16 yrs has a Karnofsky score = 60; patient = 16 yrs has a Lansky Play Performance score = 60.
7. Patient has a predicted life expectancy of = 3 months.
8. Patient has a preexisting functioning central venous catheter available for study drug administration.
9. Patient must weigh more than 3.0 kg. For patients weighing less than the 3rd percentile (based on local growth charts for age and gender) investigator judgment and consideration of overall health and growth should be used to determine participation.

For Dexamethasone PK Sampling Cyc 2: The inclusion criteria in Cyc 1 will apply to patients birth to 1 yr old entering Dexamethasone PK Sampling Cyc 2. Add. incl. criterias for the group:
- Parent/guardian (legally auth. repr.), agrees to the patient's participation as indicated by parent/legal guardian signature on the ICF.
- Patient participation in the study during a subsequent cycle of chemotherapy is considered appropriate by the investigator and will not pose unwarranted risk to the patient.
- Patient has, in the opinion of the investigator, completed the preceding cycle of chemotherapy and related study procedures satisfactorily. If a patient experiences vomiting or uses rescue medication during a study cycle, they are permitted to participate in a subsequent study cycle provided they have complied with all required study procedures.

For Optional Cyc 2-6: The inclusion criteria in Cyc 1 will apply to patients entering Cyc 2-6, with exceptions of Incl. Criteria #1, 2, 4, 6, 7 and all of the Incl. criterias in Dexamethasone PK Sampling Cyc 2 do not apply to patients entering Optional Cyc

Exclusion Criteria

For Cycle 1:
1. Patient has vomited in the 24 hrs prior to chemotherapy initiation on Treatment Day 1.
2. Patient is currently a user of any illicit drugs or has current evidence of alcohol abuse (defined using the Diagnostic and Statistical Manual-IV [DSM-IV] criteria) as determined by the investigator.
3. Patient is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant.
4. Patient has received or will receive radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period (120 hrs after chemotherapy initiation).
5. Patient is pregnant or breast feeding. (Females of reproductive potential are required to have a negative urine pregnancy test prior to entering the study.)
6. Patient is allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist.
7. Patient has a symptomatic primary or metastatic central nervous system (CNS) malignancy with nausea and/or vomiting. Patient who is asymptomatic is allowed to participate.
8.Patient has abnormal laboratory values as follows:
a. Bone Marrow Function (peripheral absolute neutrophil count <1000/mm3; Platelet count <75,000/mm3)
b. Liver Function (Aspartate aminotransferase >5.0 x upper limit of normal f(ULN) or age; Alanine aminotransferase >5.0 x ULN for age; Bilirubin >1.5 x ULN for age)
c. Renal Function (Serum creatinine >1.5 x ULN for age)
9.Patient has an active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or a history of any illness which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug or concomitant therapy to the patient.
10. Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
11. Patient has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation.
12. Patient has had benzodiazepine or opioid therapy initiated within 48 hrs of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam.
• Continuation of chronic benzodiazepine or opioid therapy is permitted provided it was initiated at least 48 hours prior to study drug administration.
13. Patient has been started on systemic corticosteroid therapy within 72 hrs prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen.
Exceptions:
• Patients who are receiving chronic (>72 hrs), daily steroid therapy can be enrolled provided the steroid dose is not >0.14 mg/kg (up to 10 mg) of prednisone daily or equivalent.
• For supportive care, patients are permitted to receive a single dose of corticosteroid within 3 days prior (but not on the day of study drug administration) provided it is less than the equivalent of 20 mg of prednisone.
14. Patient is currently taking warfarin.
15. Patient has ever participated in a study of aprepitant or fosaprepitant, or has taken a non-approved (investigational) drug within the last 4 weeks prior to randomization. Note: Patients in investigational studies with marketed chemotherapeutic agents (whether explicitly for childr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified