Chemotherapy-Induced Nausea and Vomiting
Conditions
Brief summary
The study will test aprepitant for the prevention of CINV in patients receiving their initial cycle of Moderately Emetogenic Chemotherapy (MEC). Patients receiving more then one cycle of chemotherapy may opt to participate in an optional second cycle during which the patient will receive the same antiemetic regimen as cycle 1, except that an IV formulation of aprepitant will be given in place of the oral formulation on study day one. Study drug administration on subsequent days will be given orally as in cycle 1.
Interventions
DRUGaprepitant
aprepitant 125 mg capsule; aprepitant 80 mg capsule Three day treatment period.
Ondansetron 8 mg capsule Three day treatment period.
DRUGComparator: dexamethasone
dexamethasone 12 mg tablets; 20 mg tablets Three day treatment period.
fosaprepitant dimeglumine 115 mg
DRUGComparator; Placebo (unspecified)
dexamethasone 12mg Pbo tablets.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients will be naive to emetogenic chemotherapy with histologically or cytologically confirmed malignant disease scheduled to receive a single dose of moderately emetogenic chemotherapy on study day 1 * Karnofsky score of 60 or greater
Exclusion criteria
* Patient is scheduled to receive any dose of cisplatin * Patient will receive abdominal or pelvic radiation a week prior and up to 6 days after initiation of chemotherapy * Any allergies to study drug or antiemetics * Taking CYP3A4 substrates/prohibited medication * Significant medical or mental conditions * Abnormal laboratory values (platelets, absolute neutrophils, AST, ALT, bilirubin or creatinine).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Reported No Vomiting | Overall phase (0-120 hours post initiation of MEC) in Cycle 1. | The number of patients who reported No Vomiting in the overall phase in Cycle 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Reported Complete Response | Overall phase (0-120 hours post initiation of MEC) in Cycle 1 | The number of patients who reported Complete Response (no vomiting and no use of rescue medication) in the overall phase in Cycle 1. |
Participant flow
Recruitment details
This study was conducted at 58 investigative sites worldwide. The first patient entered the study on 16-Jan- 2007 and the last patient's last visit was on 28-Oct-2008.
Pre-assignment details
Cancer patients naïve to both moderately and highly emetogenic chemotherapy (MEC and HEC, respectively) scheduled to receive an initial course of MEC for confirmed malignant disease. The study focused on patients receiving an initial cycle of MEC (Cycle 1).
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant Regimen Aprepitant 125mg by mouth (PO) plus ondansetron 8mg PO twice daily and dexamethasone 12mg PO on Day 1 and aprepitant 80mg PO once daily on Days 2 and 3. | 430 |
| Standard Regimen Ondansetron 8mg PO twice daily plus dexamethasone 20mg PO on Day 1 and ondansetron 8mg PO twice daily on Days 2 and 3. | 418 |
| Total | 848 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Total | Aprepitant Regimen | Standard Regimen |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 12.2 | 57.1 years STANDARD_DEVIATION 11.8 | 55.9 years STANDARD_DEVIATION 12.6 |
| History of Motion Sickness No | 781 Participants | 405 Participants | 376 Participants |
| History of Motion Sickness No Data - Assessment Not Completed | 2 Participants | 1 Participants | 1 Participants |
| History of Motion Sickness Yes | 65 Participants | 24 Participants | 41 Participants |
| History of Vomiting with Pregnancy No | 516 Participants | 266 Participants | 250 Participants |
| History of Vomiting with Pregnancy Not Applicable- Male Patients | 196 Participants | 103 Participants | 93 Participants |
| History of Vomiting with Pregnancy Yes | 136 Participants | 61 Participants | 75 Participants |
| Race/Ethnicity, Customized Asian | 84 participants | 49 participants | 35 participants |
| Race/Ethnicity, Customized Black | 46 participants | 26 participants | 20 participants |
| Race/Ethnicity, Customized Caucasian | 583 participants | 287 participants | 296 participants |
| Race/Ethnicity, Customized Multi-racial | 103 participants | 50 participants | 53 participants |
| Race/Ethnicity, Customized Other | 32 participants | 18 participants | 14 participants |
| Sex: Female, Male Female | 652 Participants | 327 Participants | 325 Participants |
| Sex: Female, Male Male | 196 Participants | 103 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 265 / 430 | 270 / 418 |
| serious Total, serious adverse events | 12 / 430 | 20 / 418 |
Outcome results
Primary
Number of Patients Who Reported No Vomiting
The number of patients who reported No Vomiting in the overall phase in Cycle 1
Time frame: Overall phase (0-120 hours post initiation of MEC) in Cycle 1.
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderately Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed at least one post treatment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant Regimen | Number of Patients Who Reported No Vomiting | 324 Participants |
| Standard Regimen | Number of Patients Who Reported No Vomiting | 252 Participants |
p-value: <0.01Regression, Logistic
Secondary
Number of Patients Who Reported Complete Response
The number of patients who reported Complete Response (no vomiting and no use of rescue medication) in the overall phase in Cycle 1.
Time frame: Overall phase (0-120 hours post initiation of MEC) in Cycle 1
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received MEC, (2) took a dose of study drug, and (3) completed at least one post treatment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant Regimen | Number of Patients Who Reported Complete Response | 292 Participants |
| Standard Regimen | Number of Patients Who Reported Complete Response | 229 Participants |
p-value: <0.01Regression, Logistic