Chemotherapy-induced Nausea and Vomiting
Conditions
Keywords
chemotherapy nausea vomiting
Brief summary
The purpose of the study is to mainly evaluate the efficacy and safety of aprepitant in combination with olanzapine ,palonosetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly or moderately emetogenic chemotherapy.
Detailed description
Eligible patients will be randomized to receive different antiemetic regimens . In the experimental group,patients will receive aprepitant,olanzapine ,palonosetron and dexamethasone .In the other group,patients will accept the same dose of aprepitant ,palonosetron and dexamethasone .During the treatment, any grade of nausea and vomiting should be recorded in order to evaluate the complete response rate of CINV,nausea patients will be measured by a visual analogue scale (VAS) ,other adverse events should be recorded as well.
Interventions
DRUGOlanzapine
5mg,twice a day orally on day 1 to day 4
DRUGAprepitant
125 mg capsule per oral, 1 hour before chemotherapy on day 1, 80 mg capsule daily in the morning during days 2 to 3.
DRUGPalonosetron
0.25mg IV 30-60min before chemotherapy on day 1
DRUGDexamethasone
6mg IV on day 1 ，3.75mg IV on day 2 to 4
Sponsors
Harbin Medical University
First Affiliated Hospital of Harbin Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older 2. Histologically or cytologically confirmed malignant disease 3. Accept chemotherapy for the first time 4. Patients who will receive high emetogenic cancer chemotherapy (HEC) (cisplatin\>=70mg/m2,adriamycin in combination with cyclophosphamide ,cyclophosphamide\>=1500mg/m2,adriamycin\>60mg/m2,epirubicin\>90mg/m2,dacarbazine，ifosfamide\>=2g/m2) or moderate emetogenic chemotherapy cancer (carboplatin\>=300mg/m2,cyclophosphamide\>=600-1000mg/m2,adriamycin\>50mg/m2) 5. Written informed consent
Exclusion criteria
1. Pregnant or breast-feeding 2. Uncontrolled psychosis history 3. Inability or unwillingness to understand or cooperate with study procedures 4. Central nervous system tumors primary or secondary 5. Concurrent abdominal radiotherapy 6. History of uncontrolled diabetes mellitus 7. Patients of prostatic hyperplasia ，paralytic ileus，narrow feet glaucoma. 8. Known cardiac arrhythmia, uncontrolled congestive heart failure ,or acute myocardial infarction with the previous six month 9. Pre-existing nausea or vomiting 10. Inadequate hematological function and abnormal liver and renal function. 11. History of sensitivity to olanzapine 12. Concurrent application of quinolone antibiotic therapy 13. Treatment with another antipsychotic agent such as risperidone,quetiapine, clozapine,phenothiazine,or butyrophenone for 30 days prior to or during the chemotherapy. 14. Cytochrome P450 3A4 substrates within 7 days (terfenadine, cisapride, astemizole, pimozide) 15. Concurrent application of systemic corticosteroids 16. Active infection or gastrointestinal dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Receiving HEC With Complete Response in Overall Phase | 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. |
| Proportion of Participants Receiving MEC With Complete Response in Overall Phase | 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 Receiving HEC With No Vomiting in the Overall Phase | 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 Receiving HEC With No Vomiting in the Acute Phase | 0 to 24 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 ） |
| Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase | 24 to 120 hours | Overall Phase was defined as 24 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 Receiving MEC With Complete Response in the Acute Phase | 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 Receiving HEC With Complete Response in the Acute Phase | 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 Receiving MEC With No Vomiting in the Overall Phase | 0-120 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 Receiving MEC With No Vomiting in the Acute Phase | 0 to 24 hours | Overall Phase was defined as 0 to 24 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 Receiving MEC With No Vomiting in the Delayed Phase | 24 to 120 hours | Overall Phase was defined as 24 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 Receiving MEC With Complete Response in the Delayed Phase | 24 to 120 hours | Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. |
| Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase | 24 to 120 hours | Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine Regimen Olanzapine in combination with aprepitant ,palonosetron and dexamethasone.
Olanzapine: 5mg,twice a day orally on day 1 to day 4
Aprepitant: 125 mg capsule per oral, 1 hour before chemotherapy on day 1, 80 mg capsule daily in the morning during days 2 to 3.
Palonosetron: 0.25mg IV 30-60min before chemotherapy on day 1
Dexamethasone: 6mg IV on day 1 ，3.75mg IV on day 2 to 4 | 56 |
| Control Regimen Aprepitant in combination with palonosetron and dexamethasone
Aprepitant: 125 mg capsule per oral, 1 hour before chemotherapy on day 1, 80 mg capsule daily in the morning during days 2 to 3.
Palonosetron: 0.25mg IV 30-60min before chemotherapy on day 1
Dexamethasone: 6mg IV on day 1 ，3.75mg IV on day 2 to 4 | 58 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Olanzapine Regimen | Control Regimen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 49 Participants | 96 Participants |
| Age, Continuous | 55.43 years STANDARD_DEVIATION 9.55 | 52.98 years STANDARD_DEVIATION 10.81 | 54.18 years STANDARD_DEVIATION 10.24 |
| History of drinking NO | 41 participants | 49 participants | 90 participants |
| History of drinking YES | 15 participants | 9 participants | 24 participants |
| Region of Enrollment China | 56 participants | 56 participants | 114 participants |
| Sex: Female, Male Female | 33 Participants | 37 Participants | 70 Participants |
| Sex: Female, Male Male | 23 Participants | 21 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 58 |
| other Total, other adverse events | 21 / 56 | 14 / 58 |
| serious Total, serious adverse events | 0 / 56 | 0 / 58 |
Outcome results
Primary
Proportion of Participants Receiving HEC With Complete Response in Overall Phase
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: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With Complete Response in Overall Phase | 20 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With Complete Response in Overall Phase | 15 Participants |
p-value: 0.397Chi-squared
Primary
Proportion of Participants Receiving MEC With Complete Response in Overall Phase
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: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With Complete Response in Overall Phase | 36 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With Complete Response in Overall Phase | 40 Participants |
p-value: 1Chi-squared
Secondary
Proportion of Participants Receiving HEC With Complete Response in the Acute Phase
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: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With Complete Response in the Acute Phase | 20 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With Complete Response in the Acute Phase | 17 Participants |
Secondary
Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase
Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
Time frame: 24 to 120 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase | 20 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase | 15 Participants |
p-value: 0.397Chi-squared
Secondary
Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase
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 ）
Time frame: 0 to 24 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase | 18 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase | 15 Participants |
p-value: 1Chi-squared
Secondary
Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase
Overall Phase was defined as 24 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: 24 to 120 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase | 17 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase | 7 Participants |
p-value: 0.005Chi-squared
Secondary
Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase
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: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received High Emetogenic Chemotherapy (HEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase | 17 Participants |
| Control Regimen | Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase | 6 Participants |
p-value: 0.02Chi-squared
Secondary
Proportion of Participants Receiving MEC With Complete Response in the Acute Phase
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: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With Complete Response in the Acute Phase | 36 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With Complete Response in the Acute Phase | 41 Participants |
Secondary
Proportion of Participants Receiving MEC With Complete Response in the Delayed Phase
Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
Time frame: 24 to 120 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With Complete Response in the Delayed Phase | 36 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With Complete Response in the Delayed Phase | 40 Participants |
p-value: 1Chi-squared
Secondary
Proportion of Participants Receiving MEC With No Vomiting in the Acute Phase
Overall Phase was defined as 0 to 24 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 24 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Acute Phase | 35 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Acute Phase | 40 Participants |
p-value: 1Chi-squared
Secondary
Proportion of Participants Receiving MEC With No Vomiting in the Delayed Phase
Overall Phase was defined as 24 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: 24 to 120 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Delayed Phase | 30 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Delayed Phase | 31 Participants |
p-value: 0.246Chi-squared
Secondary
Proportion of Participants Receiving MEC With No Vomiting in the Overall Phase
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: 0-120 hours
Population: FAS (full analysis set) patient population was used for all efficacy evaluations and included patients who (1) received Moderate Emetogenic Chemotherapy (MEC), (2) took a dose of study drug, and (3) completed treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olanzapine Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Overall Phase | 30 Participants |
| Control Regimen | Proportion of Participants Receiving MEC With No Vomiting in the Overall Phase | 30 Participants |
p-value: 0.283Chi-squared