Gynecologic Cancer
Conditions
Brief summary
The objective of this study is to investigate the efficacy of olanzapine as compared to neurokinin-1 receptor antagonists (NK1-RAs) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic malignancies receiving single day outpatient chemotherapy (carboplatin and paclitaxel) every 3 weeks.
Interventions
DRUGOndansetron
8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy
DRUGDexamethasone
20 mg IV on day 1 pre-chemotherapy
DRUGNeurokinin-1 Receptor Antagonist (NK1-RA)
150 mg IV on day 1 pre-chemotherapy
DRUGOlanzapine
5 mg by mouth on days 1-4 of chemotherapy (taken at night)
DRUGCompazine
5-10 mg by mouth, available as needed, every 6 hours, days 1-5
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of gynecologic malignancy * No chemotherapy in the last 12 months * Scheduled to receive Carboplatin (AUC\>=4) and Paclitaxel every three weeks * ECOG performance status 0 or 1 * English speaking * Willing and able to provide informed consent * Laboratory values within protocol-defined parameters * No vomiting in the 24 hours prior to initiating chemotherapy * If childbearing potential exists, negative pregnancy test within 7 days prior to registration
Exclusion criteria
* Significant cognitive compromise * History of CNS disease (e.g. brain metastases, seizure disorder, dementia) * Current or recent (within 30 days) treatment with another antipsychotic agent (antidepressant medications are OK) * Concurrent radiotherapy treatment * Known hypersensitivity to olanzapine * Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the last six months * History of diabetes mellitus on medication (insulin or oral glycemic agent) * Alcohol abuse / chronic alcoholism * History of closed angle glaucoma * Current enrollment in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Response in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 120 hours post initiating chemotherapy during cycle 1 | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Response in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 24-120 hours post initiating chemotherapy during cycle 1 | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. |
| Rate of no Nausea in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 24 hours post initiating chemotherapy during cycle 1 | Patients will record daily levels of nausea after chemotherapy using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). |
| Rate of no Nausea in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 120 hours post initiating chemotherapy during cycle 1 | Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). |
| Rate of Complete Response in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 24 hours post initiating chemotherapy during cycle 1 | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. |
| Mean Somnolence Score | assessed daily, and reported at day 6 post final study treatment | Patients will record daily levels of undesired sedation using a Likert scale ranging from 0 to 10 (0 indicating no undesired sedation; 10 indicating maximum level of undesired sedation). |
| Mean Increased-appetite Score | assessed daily, and reported at day 6 post final study treatment | Patients will record daily levels of undesired increase in appetite using a Likert scale ranging from 0 to 10 (0 indicating no undesired increase in appetite; 10 indicating maximum level of undesired increase in appetite). |
| Rate of no Nausea in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 120 hours post initiating chemotherapy during cycle 1 | Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nk1-RA Nk1-RA will be given on day 1 of each 3-week chemotherapy cycle, for up to 6 cycles.
Ondansetron: 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy
Dexamethasone: 20 mg IV on day 1 pre-chemotherapy
Neurokinin-1 Receptor Antagonist (NK1-RA): 150 mg IV on day 1 pre-chemotherapy
Compazine: 5-10 mg by mouth, available as needed, every 6 hours, days 1-5 | 27 |
| Olanzapine Olanzapine will be given on days 1-4 of each 3-week chemotherapy cycle, for up to 6 cycles.
Ondansetron: 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy
Dexamethasone: 20 mg IV on day 1 pre-chemotherapy
Olanzapine: 5 mg by mouth on days 1-4 of chemotherapy (taken at night)
Compazine: 5-10 mg by mouth, available as needed, every 6 hours, days 1-5 | 24 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Incomplete data | 4 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Nk1-RA | Total | Olanzapine |
|---|---|---|---|
| Age, Customized Age | 69 years | 69 years | 72 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 25 Participants | 48 Participants | 23 Participants |
| Region of Enrollment United States | 27 participants | 51 participants | 24 participants |
| Sex: Female, Male Female | 27 Participants | 51 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 27 | 6 / 24 |
| other Total, other adverse events | 24 / 27 | 23 / 24 |
| serious Total, serious adverse events | 3 / 27 | 5 / 24 |
Outcome results
Primary
Rate of Complete Response in the Overall Time Period (0 - 120 Hours Post-chemotherapy)
Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.
Time frame: 120 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of Complete Response in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 11 Participants |
| Olanzapine | Rate of Complete Response in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 14 Participants |
Secondary
Mean Increased-appetite Score
Patients will record daily levels of undesired increase in appetite using a Likert scale ranging from 0 to 10 (0 indicating no undesired increase in appetite; 10 indicating maximum level of undesired increase in appetite).
Time frame: assessed daily, and reported at day 6 post final study treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Nk1-RA | Mean Increased-appetite Score | 0.45 score on a scale |
| Olanzapine | Mean Increased-appetite Score | 0.33 score on a scale |
Secondary
Mean Somnolence Score
Patients will record daily levels of undesired sedation using a Likert scale ranging from 0 to 10 (0 indicating no undesired sedation; 10 indicating maximum level of undesired sedation).
Time frame: assessed daily, and reported at day 6 post final study treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Nk1-RA | Mean Somnolence Score | 0.81 score on a scale |
| Olanzapine | Mean Somnolence Score | 1.15 score on a scale |
Secondary
Rate of Complete Response in the Acute Time Period (0 - 24 Hours Post-chemotherapy)
Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.
Time frame: 24 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of Complete Response in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 19 Participants |
| Olanzapine | Rate of Complete Response in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 22 Participants |
Secondary
Rate of Complete Response in the Delayed Time Period (24 - 120 Hours Post-chemotherapy)
Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.
Time frame: 24-120 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of Complete Response in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 14 Participants |
| Olanzapine | Rate of Complete Response in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 14 Participants |
Secondary
Rate of no Nausea in the Acute Time Period (0 - 24 Hours Post-chemotherapy)
Patients will record daily levels of nausea after chemotherapy using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).
Time frame: 24 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of no Nausea in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 17 Participants |
| Olanzapine | Rate of no Nausea in the Acute Time Period (0 - 24 Hours Post-chemotherapy) | 19 Participants |
Secondary
Rate of no Nausea in the Delayed Time Period (24 - 120 Hours Post-chemotherapy)
Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).
Time frame: 120 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of no Nausea in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 10 Participants |
| Olanzapine | Rate of no Nausea in the Delayed Time Period (24 - 120 Hours Post-chemotherapy) | 8 Participants |
Secondary
Rate of no Nausea in the Overall Time Period (0 - 120 Hours Post-chemotherapy)
Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).
Time frame: 120 hours post initiating chemotherapy during cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nk1-RA | Rate of no Nausea in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 9 Participants |
| Olanzapine | Rate of no Nausea in the Overall Time Period (0 - 120 Hours Post-chemotherapy) | 6 Participants |