Chemotherapy-induced Nausea and Vomiting (CINV)
Conditions
Keywords
CINV
Brief summary
This study will demonstrate and confirm the efficacy and safety of MK0869 for the treatment of chemotherapy-induced nausea and vomiting in Chinese patients.
Interventions
DRUGaprepitant
Day 1: Oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Oral aprepitant 80 mg
DRUGComparator: Placebo to aprepitant
Day 1: Placebo to oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Placebo to oral aprepitant 80 mg
DRUGdexamethasone
Day 1: Oral dexamethasone 10.5 mg prior to administration of cisplatin; Days 2, 3, and 4: Oral dexamethasone 7.5 mg
DRUGgranisetron
Day 1: IV granisetron 3 mg prior to administration of cisplatin
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cycle 1: * Patient is scheduled to receive his/her first course of cisplatin chemotherapy at a dose of at least 70 mg/m\^2 administered a maximum of 3 hours * Patient has a predicted life expectancy of at least 3 months * Patient is not pregnant Cycle 2 (optional): * Participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator and will not pose unwarranted risk to the patient. * Satisfactory completion of the preceding cycle of chemotherapy and related study procedures. * Patient will continue to receive the same chemotherapy regimen as in Cycle 1. The cisplatin dose may be reduced in subsequent cycle, as long as the new dose is still no less than 70 mg/m\^2.
Exclusion criteria
Cycles 1 & 2: * Patient will receive stem cell therapy in conjunction with cisplatin * Patient has an active infection or any uncontrolled disease (e.g. diabetes) * Patient will receive multiple-day chemotherapy with cisplatin * Patient will receive chemotherapy of moderate or high emetogenicity on the 6 days prior to cisplatin infusion or the 6 days following the cisplatin infusion * Patient has vomited within 24 hours prior to cisplatin infusion * Patient received or will receive radiation therapy to the abdomen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Complete Response 120 Hours Following Initiation of High-dose Cisplatin Chemotherapy in the Overall Phase of Cycle 1 | 0 to 120 hours | Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Complete Response in the Acute Phase of Cycle 1 | 0 to 24 hours | Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. |
| Proportion of Participants With No Vomiting in the Overall Phase of Cycle 1 | 0 to 120 hours | Overall Phase was defined as 0 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). |
| Proportion of Participants With No Vomiting in the Acute Phase of Cycle 1 | 0 to 24 hours | Acute Phase was defined as 0 to 24 hours following initiation of chemotherapy. |
| Proportion of Participants With Complete Response in the Delayed Phase of Cycle 1 | 25 to 120 hours | Delayed phase was defined as 25 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. |
| Proportion of Participants With No Impact on Daily Life in Cycle 1 | 0 to 120 hours | The Functional Living Index-Emesis is a self-administered, validated emesis & nausea-specific questionnaire. Participants completed the questionnaire 5 days post chemotherapy. It had 9 questions each on nausea and vomiting. No impact of chemotherapy-induced nausea & vomiting (CINV) on daily life was defined as an average item score of \>6 on the 7-point scale (i.e., \>108 total score). The scale was in the opposite direction for questions 3, 6, 11, 15 & 18. For each question: score ranged from 1 (worst) to 7 (best, i.e., no CINV). Total score range was 7 (worst) to 126 (best). |
| Time to First Vomiting Episode in Cycle 1 | 0 to 120 hours | Time from administration of chemotherapy to first vomiting episode. |
| Proportion of Participants With No Vomiting in the Delayed Phase of Cycle 1 | 25 to 120 hours | Delayed Phase was defined as 25 to 120 hours following initiation of chemotherapy |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant (MK-0869) Day 1: Oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Oral aprepitant 80 mg
Day 1: Intravenous (IV) granisetron 3 mg prior to administration of cisplatin
Day 1: oral dexamethasone 6 mg prior to the administration of cisplatin; Days 2 and 3: oral dexamethasone 3.75 mg | 209 |
| Placebo Day 1: Placebo to oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Placebo to oral aprepitant 80 mg
Day 1: Oral dexamethasone 10.5 mg prior to administration of cisplatin; Days 2, 3, and 4: Oral dexamethasone 7.5 mg
Day 1: IV granisetron 3 mg prior to administration of cisplatin | 212 |
| Total | 421 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Cycle 1 | Adverse Event | 4 | 1 |
| Cycle 1 | Lost to Follow-up | 11 | 2 |
| Cycle 1 | Physician Decision | 0 | 1 |
| Cycle 1 | Protocol Violation | 2 | 1 |
| Cycle 1 | Withdrawal by Subject | 3 | 8 |
| Cycle 2 | Lost to Follow-up | 6 | 9 |
| Cycle 2 | Physician Decision | 1 | 1 |
| Cycle 2 | Progressive Disease | 0 | 1 |
| Cycle 2 | Protocol Violation | 1 | 0 |
| Cycle 2 | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Aprepitant (MK-0869) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 10.1 | 53.6 years STANDARD_DEVIATION 10.6 | 53.4 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment China | 209 participants | 212 participants | 421 participants |
| Sex: Female, Male Female | 71 Participants | 73 Participants | 144 Participants |
| Sex: Female, Male Male | 138 Participants | 139 Participants | 277 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 123 / 205 | 124 / 210 |
| serious Total, serious adverse events | 5 / 205 | 2 / 210 |
Outcome results
Primary
Proportion of Participants With Complete Response 120 Hours Following Initiation of High-dose Cisplatin Chemotherapy in the Overall Phase of Cycle 1
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
Time frame: 0 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With Complete Response 120 Hours Following Initiation of High-dose Cisplatin Chemotherapy in the Overall Phase of Cycle 1 | 0.696 Proportion of participants |
| Placebo | Proportion of Participants With Complete Response 120 Hours Following Initiation of High-dose Cisplatin Chemotherapy in the Overall Phase of Cycle 1 | 0.570 Proportion of participants |
Comparison: Adjusted by gender and concomitant~chemotherapy.~The apriori significance level was set at 0.05.~There was no adjustment for multiplicity.p-value: 0.007Regression, Logistic
Secondary
Proportion of Participants With Complete Response in the Acute Phase of Cycle 1
Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
Time frame: 0 to 24 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With Complete Response in the Acute Phase of Cycle 1 | 0.794 Proportion of participants |
| Placebo | Proportion of Participants With Complete Response in the Acute Phase of Cycle 1 | 0.793 Proportion of participants |
Comparison: Adjusted by gender and concomitant chemotherapy.~The apriori significance level was set at 0.05.~There was no adjustment for multiplicity.p-value: 0.942Regression, Logistic
Secondary
Proportion of Participants With Complete Response in the Delayed Phase of Cycle 1
Delayed phase was defined as 25 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
Time frame: 25 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With Complete Response in the Delayed Phase of Cycle 1 | 0.740 Proportion of participants |
| Placebo | Proportion of Participants With Complete Response in the Delayed Phase of Cycle 1 | 0.594 Proportion of participants |
Comparison: Adjusted by gender and concomitant chemotherapy.~The apriori significance level was set at 0.05.~There was no adjustment for multiplicity.p-value: 0.001Regression, Logistic
Secondary
Proportion of Participants With No Impact on Daily Life in Cycle 1
The Functional Living Index-Emesis is a self-administered, validated emesis & nausea-specific questionnaire. Participants completed the questionnaire 5 days post chemotherapy. It had 9 questions each on nausea and vomiting. No impact of chemotherapy-induced nausea & vomiting (CINV) on daily life was defined as an average item score of \>6 on the 7-point scale (i.e., \>108 total score). The scale was in the opposite direction for questions 3, 6, 11, 15 & 18. For each question: score ranged from 1 (worst) to 7 (best, i.e., no CINV). Total score range was 7 (worst) to 126 (best).
Time frame: 0 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With No Impact on Daily Life in Cycle 1 | 0.705 Proportion of participants |
| Placebo | Proportion of Participants With No Impact on Daily Life in Cycle 1 | 0.683 Proportion of participants |
Secondary
Proportion of Participants With No Vomiting in the Acute Phase of Cycle 1
Acute Phase was defined as 0 to 24 hours following initiation of chemotherapy.
Time frame: 0 to 24 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With No Vomiting in the Acute Phase of Cycle 1 | 0.804 Proportion of participants |
| Placebo | Proportion of Participants With No Vomiting in the Acute Phase of Cycle 1 | 0.798 Proportion of participants |
Comparison: Adjusted by gender and concomitant chemotherapy.p-value: 0.882Regression, Logistic
Secondary
Proportion of Participants With No Vomiting in the Delayed Phase of Cycle 1
Delayed Phase was defined as 25 to 120 hours following initiation of chemotherapy
Time frame: 25 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With No Vomiting in the Delayed Phase of Cycle 1 | 0.740 Proportion of participants |
| Placebo | Proportion of Participants With No Vomiting in the Delayed Phase of Cycle 1 | 0.594 Proportion of participants |
Comparison: Adjusted by gender and concomitant chemotherapy.p-value: 0.001Regression, Logistic
Secondary
Proportion of Participants With No Vomiting in the Overall Phase of Cycle 1
Overall Phase was defined as 0 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy).
Time frame: 0 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant (MK-0869) | Proportion of Participants With No Vomiting in the Overall Phase of Cycle 1 | 0.706 Proportion of participants |
| Placebo | Proportion of Participants With No Vomiting in the Overall Phase of Cycle 1 | 0.570 Proportion of participants |
Comparison: Adjusted by gender and concomitant~chemotherapy.p-value: 0.003Regression, Logistic
Secondary
Time to First Vomiting Episode in Cycle 1
Time from administration of chemotherapy to first vomiting episode.
Time frame: 0 to 120 hours
Population: Full Analysis Set (FAS), defined as those who received chemotherapy, received a dose of study drug and had at least one post-treatment assessment. Any participant who did not have a response recorded for the assessment was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant (MK-0869) | Time to First Vomiting Episode in Cycle 1 | 77.0 Hours | Standard Error 2.5 |
| Placebo | Time to First Vomiting Episode in Cycle 1 | 76.0 Hours | Standard Error 2.8 |