Chemotherapy-Induced Nausea and Vomiting (CINV)
Conditions
Brief summary
The purpose of this study is to examine the safety, tolerability, and efficacy of MK0517 to prevent Chemotherapy-Induced Nausea and Vomiting (CINV) associated with Cisplatin chemotherapy.
Interventions
single IV dose of 150 mg of fosaprepitant dimeglumine on Day 1.
DRUGComparator: Aprepitant
Aprepitant 3-day dosing oral regimen (125 mg on Day 1 followed by 80 mg on Days 2 and 3).
DRUGDexamethasone
Oral dose of 12 mg of dexamethasone on Day 1, 8 mg on Day 2, and 8 mg twice a day on Days 3-4.
DRUGOndansetron
single IV dose of 32 mg of ondansetron on Day 1.
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
* Patient is male or female and is at least 18 years of age; scheduled to receive his or her first course of cisplatin chemotherapy at a dose of 70 mg/m2 or higher; predicted life expectancy of 3 months or greater * Patient is post menopausal or, if premenopausal, must use double-barrier contraception
Exclusion criteria
* Patient has symptomatic primary or metastatic CNS malignancy * Patient has received or will receive Radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 though Day 6 * Patient has vomited in the 24 hours prior to treatment Day 1 * Patient has an active infection; Patient uses illicit drugs or has current evidence of alcohol abuse * Patient is pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A Complete Response (no Vomiting and no Use of Rescue Therapy) Overall (in the 120 Hours Following Initiation of Cisplatin). | Overall (in the 120 hours following initiation of cisplatin chemotherapy). | The number of patients who reported No Vomiting and No Use of Rescue Therapy in the 120 hours following initiation of cisplatin chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A Complete Response (no Vomiting and no Use of Rescue Therapy) in the Delayed Phase (25 to 120 Hours Following Initiation of Cisplatin). | Delayed phase (25 to 120 hours following initiation of cisplatin). | The number of patients who reported No Vomiting and No Use of Rescue Therapy in the 25 to 120 hours following initiation of cisplatin chemotherapy. |
| No Vomiting Overall (in the 120 Hours Following Initiation of Cisplatin) | Overall (the 120 hours following initiation of cisplatin chemotherapy) | The number of patients who reported No Vomiting in the 120 hours following initiation of cisplatin chemotherapy. |
Participant flow
Recruitment details
Patients were recruited from 149 medical centers worldwide. The recruitment period was from 12 Feb 08 through 8 Jun 09.
Pre-assignment details
Cisplatin-naïve patients scheduled to receive cisplatin chemotherapy at a dose of 70 mg/m2 or higher for a documented solid malignancy were screened up to 30 days prior to initiation of chemotherapy. Screening included a complete medical history and physical exam. Informed consent was obtained for patients who agreed to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Fosaprepitant Fosaprepitant dimeglumine 150 mg IV, ondansetron 32 mg IV, and dexamethasone 12 mg by mouth (PO) on Day 1, dexamethasone 8 mg PO on Day 2, and dexamethasone 16 mg PO on Days 3 and 4. | 1,147 |
| Aprepitant Aprepitant 125 mg by mouth (PO), ondansetron 32 mg IV, and dexamethasone 12 mg PO on Day 1, aprepitant 80 mg PO and dexamethasone 8 mg PO on Days 2 and 3, dexamethasone 8 mg PO on Day 4. | 1,175 |
| Total | 2,322 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 32 | 36 |
| Overall Study | Lost to Follow-up | 12 | 16 |
| Overall Study | Physician Decision | 0 | 7 |
| Overall Study | Progressive Disease | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 20 |
Baseline characteristics
| Characteristic | Aprepitant | Fosaprepitant | Total |
|---|---|---|---|
| Age, Continuous | 55.9 years | 55.2 years | 55.6 years |
| History of Motion Sickness No | 1166 Participants | 1143 Participants | 2309 Participants |
| History of Motion Sickness No Data - Assessment Not Completed | 6 Participants | 4 Participants | 10 Participants |
| History of Motion Sickness Yes | 3 Participants | 0 Participants | 3 Participants |
| History of Vomiting with Pregnancy Female Patients with No Data - No Assessment | 3 Participants | 2 Participants | 5 Participants |
| History of Vomiting with Pregnancy No | 421 Participants | 420 Participants | 841 Participants |
| History of Vomiting with Pregnancy Not Applicable - Male Patients | 748 Participants | 722 Participants | 1470 Participants |
| History of Vomiting with Pregnancy Yes | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 33 participants | 32 participants | 65 participants |
| Race/Ethnicity, Customized Asian | 306 participants | 296 participants | 602 participants |
| Race/Ethnicity, Customized Black or African American | 22 participants | 21 participants | 43 participants |
| Race/Ethnicity, Customized Multi-Racial | 157 participants | 149 participants | 306 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized White | 655 participants | 648 participants | 1303 participants |
| Sex: Female, Male Female | 427 Participants | 425 Participants | 852 Participants |
| Sex: Female, Male Male | 748 Participants | 722 Participants | 1470 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 636 / 1,143 | 679 / 1,169 |
| serious Total, serious adverse events | 148 / 1,143 | 157 / 1,169 |
Outcome results
Primary
A Complete Response (no Vomiting and no Use of Rescue Therapy) Overall (in the 120 Hours Following Initiation of Cisplatin).
The number of patients who reported No Vomiting and No Use of Rescue Therapy in the 120 hours following initiation of cisplatin chemotherapy.
Time frame: Overall (in the 120 hours following initiation of cisplatin chemotherapy).
Population: FAS (Full Analysis Set) patient population was used for all efficacy evaluations and included patients who: 1) received at least one dose of study therapy, 2) received cisplatin chemotherapy, and 3) had at least one post-treatment efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant | A Complete Response (no Vomiting and no Use of Rescue Therapy) Overall (in the 120 Hours Following Initiation of Cisplatin). | 795 Participants |
| Aprepitant | A Complete Response (no Vomiting and no Use of Rescue Therapy) Overall (in the 120 Hours Following Initiation of Cisplatin). | 820 Participants |
95% CI: [-4.1, 3.3]
Secondary
A Complete Response (no Vomiting and no Use of Rescue Therapy) in the Delayed Phase (25 to 120 Hours Following Initiation of Cisplatin).
The number of patients who reported No Vomiting and No Use of Rescue Therapy in the 25 to 120 hours following initiation of cisplatin chemotherapy.
Time frame: Delayed phase (25 to 120 hours following initiation of cisplatin).
Population: FAS (Full Analysis Set) patient population was used for all efficacy evaluations and included patients who: 1) received at least one dose of study therapy, 2) received cisplatin chemotherapy, and 3) had at least one post-treatment efficacy assessment. 1 patient (aprepitant group) had no delayed phase data, and was not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant | A Complete Response (no Vomiting and no Use of Rescue Therapy) in the Delayed Phase (25 to 120 Hours Following Initiation of Cisplatin). | 822 Participants |
| Aprepitant | A Complete Response (no Vomiting and no Use of Rescue Therapy) in the Delayed Phase (25 to 120 Hours Following Initiation of Cisplatin). | 841 Participants |
95% CI: [-3.5, 3.7]
Secondary
No Vomiting Overall (in the 120 Hours Following Initiation of Cisplatin)
The number of patients who reported No Vomiting in the 120 hours following initiation of cisplatin chemotherapy.
Time frame: Overall (the 120 hours following initiation of cisplatin chemotherapy)
Population: FAS (Full Analysis Set) patient population was used for all efficacy evaluations and included patients who: 1) received at least one dose of study therapy, 2) received cisplatin chemotherapy, and 3) had at least one post-treatment efficacy assessment. 2 patients (aprepitant group) had no vomiting data, and were excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant | No Vomiting Overall (in the 120 Hours Following Initiation of Cisplatin) | 806 Participants |
| Aprepitant | No Vomiting Overall (in the 120 Hours Following Initiation of Cisplatin) | 844 Participants |
95% CI: [-5.3, 2]