Breast Carcinoma
Conditions
Brief summary
This randomized phase III trial studies how well netupitant/palonosetron hydrochloride and dexamethasone with prochlorperazine or olanzapine work compared to netupitant/palonosetron hydrochloride and dexamethasone in improving chemotherapy-induced nausea and vomiting in patients with breast cancer. Antiemetic drugs, such as prochlorperazine and olanzapine, may help lessen nausea and vomiting in patients with breast cancer treated with chemotherapy.
Detailed description
PRIMARY OBJECTIVES: I. To determine if control of nausea at cycle 2 in participants who experienced chemotherapy-induced nausea and vomiting (CINV) at cycle 1 is improved by the addition of either prochlorperazine or olanzapine to the control arm of netupitant, palonosetron and dexamethasone. SECONDARY OBJECTIVES: I. To determine if olanzapine is more effective than prochlorperazine in controlling nausea at cycle 2 in participants who experienced CINV at cycle 1 when used in combination with netupitant, palonosetron and dexamethasone. II. To determine if control of vomiting at cycle 2 in patients who experienced CINV at cycle 1 is improved by the addition of either prochlorperazine or olanzapine to the control arm of netupitant, palonosetron and dexamethasone. III. To determine if olanzapine is more effective than prochlorperazine in controlling vomiting at cycle 2 in participants who experienced CINV at cycle 1 when used in combination with netupitant, palonosetron and dexamethasone. TERTIARY OBJECTIVES: I. To create an empirically-based algorithm predicting nausea from breast cancer chemotherapy regimens that takes into account not only state-of-the-art anti-emetic regimens but also participant factors such as age, race, education, ethnicity, quality of life (QOL), alcohol consumption, susceptibility to nausea, expectancy, anxiety, level of nausea on the day prior to treatment, and prior history of nausea. II. To compare the effects of the interventions on QOL, as assessed by the Functional Assessment of Cancer Therapy- General (FACT-G), by following the same procedures described under the primary aim and the first secondary aim, using change in the FACT-G scores as the response. III. To provide preliminary data on the frequency and severity of sleep disturbance, fatigue, anxiety, and dizziness, across treatment conditions. IV. To provide preliminary data on biological factors (e.g. glutathione \[GSH\] recycling, genetic markers) that may help identify a subgroup of patients at high risk for development of cancer-related or treatment-related side effects, or response to treatment. OUTLINE: PART I: Patients receive 1 cycle of standard of care chemotherapy. PART II: Patients with a nausea score \>= 3 at least once on the diary at cycle 1 chemotherapy are randomized into 1 of 3 groups at cycle 2. GROUP I: Within 1 hour prior to chemotherapy, patients receive netupitant/palonosetron hydrochloride orally (PO) on day 1. Within 30 minutes prior to chemotherapy, patients also receive dexamethasone PO on days 1-4. Patients also receive placebo PO with chemotherapy every 8 hours (Q8H) on days 1-4. GROUP II: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive prochlorperazine PO Q8H and placebo PO with chemotherapy on days 1-4. GROUP III: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive olanzapine PO and placebo PO Q8H with chemotherapy on days 1-4. After completion of study treatment, patients are followed up for 30 days.
Interventions
DRUGDexamethasone
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGNetupitant/Palonosetron Hydrochloride
Given PO
DRUGOlanzapine
Given PO
OTHERPlacebo
Given PO
DRUGProchlorperazine
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
University of Rochester NCORP Research Base
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of breast cancer and be chemotherapy naive; NOTE: prior methotrexate for non-cancerous conditions is allowed * Be scheduled to receive a single-day chemotherapy regimen that contains doxorubicin and/or cyclophosphamide and/or carboplatin. Single-day chemotherapy is defined as only one infusion or injection per cycle. Herceptin (trastuzumab) and other chemotherapy agents will be allowed with any of these regimens * Be scheduled to receive an antiemetic regimen that does not contain Akynzeo; in addition, the antiemetic regimen must conform with American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines at cycle 1 * Be able to read English * Have the ability to give written informed consent * Have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * NOTE: patients 80 years of age or older must have approval from an oncologist or their designee to participate in this study * NOTE: patients currently receiving warfarin must have approval from an oncologist or their designee to participate in this study * Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, or abstinence) for the duration of the study and have a negative pregnancy test within 10 days prior to the initiation of chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately * CYCLE II PORTION ONLY: Only participants with a nausea score \>= 3 at least once on the diary assessment from cycle 1 can be randomized for cycle 2 * CYCLE II PORTION ONLY: Participants must be scheduled to receive the same chemotherapy regimen as received at cycle 1
Exclusion criteria
* Have clinical evidence of current or impending bowel obstruction * Have a known history of central nervous system disease (e.g., brain metastases or a seizure disorder) * Have dementia * Have uncontrolled diabetes mellitus or uncontrolled hyperglycemia * Have severe hepatic impairment, severe renal impairment, or end-stage renal disease as determined by the treating physician * Have had long term treatment (\> 5 days within the past 30 days) with an antipsychotic agent such as risperidone, quetiapine, clozapine, a phenothiazine, or a butyrophenone within 30 days before enrollment or plans for such treatment during the study period; NOTE: participants could have received prochlorperazine and other phenothiazines as antiemetic therapy on a short term basis (i.e., =\< 5 days) * Have a known cardiac arrhythmia, uncontrolled congestive heart failure, or acute myocardial infarction within the previous 6 months * Be taking benzodiazepines regularly (\> 5 days within the past 30 days); pro re nata (PRN) use (=\< 5 days) for the short-term relief of the symptoms of anxiety, anxiety associated with depressive symptoms, or as a rescue medication for breakthrough CINV is allowed * Be taking anticholinergic medications * Be receiving quinolone antibiotic therapy * Be taking amifostine (Ethiofos) * Have a known hypersensitivity to olanzapine or to phenothiazines * CYCLE II PORTION ONLY: Must not have received Akynzeo at cycle 1 * CYCLE II PORTION ONLY: Must still meet all the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4) | Will be measured on a 7-point scale (1: not at all nauseated, 4: moderately nauseated, 7: extremely nauseated). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night). |
| Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4) | Will be measured on a 7-point scale (1: not at all nauseated, 4: moderately nauseated, 7: extremely nauseated). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4) | Will be measured on a 7-point scale anchored by 1:not at all nauseated and 7:extremely nauseated. Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 and 16 assessment points for Cycle 2. This will be assessed by estimating the contrast D = (3 - 1) - (2 - 1), where 3 is the Arm 3 mean, 2 is the Arm 2 mean, and 1 is the Control mean. |
| Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Vomiting measured at Cycle 1 Chemotherapy (Yes/No on Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (Yes/No on Days 1,2,3,4) | The response variable will be Any VOMITING (yes/no) after Cycle 2 Chemotherapy, treatment arm as the main factor, and Any Vomiting after Cycle 1 as a covariate. Estimation will be performed using maximum likelihood assuming a binomial distribution and logit link. The same group of contrasts described in the Primary Aim analysis will be estimated and tested, with a significance level of 0.025 to adjust for multiple tests. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Regimens: Chemotherapy Regimens at Cycle 2 | Cycle 2 Chemotherapy | Grouping of Chemotherapy Regimens at Cycle 2 |
| Emetogenic Potential | Cycle 2 Chemotherapy | Emetogenic Potential: The percentage of risk of vomiting based on given chemotherapy agents. Reference: https://pubmed.ncbi.nlm.nih.gov/38129530/ |
| Vomiting at Cycle 1 of Chemotherapy | Cycle 1 Chemotherapy | Record of any vomiting (Yes/No) during Cycle 1 of Chemotherapy on Days 1, 2, 3, 4 |
| Vomiting at Cycle 2 of Chemotherapy | Cycle 2 Chemotherapy | Record of any vomiting (Yes/No) during Cycle 2 of Chemotherapy on Days 1, 2, 3, 4 |
Countries
United States
Participant flow
Pre-assignment details
1363 subjects were enrolled. CYCLE 1 which is the First Chemotherapy Cycle (excluded 796 \[5 registration errors, 41 no four-day home record, 750 did not have average score of 3 or better\]) CYCLE 2 which is the Second Chemotherapy Cycle (excluded 250 \[subject decided not to continue on cycle 2\]). 317 subjects are available for randomization. 310 subjects were actually randomized.
Participants by arm
| Arm | Count |
|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone Within 1 hour prior to chemotherapy, patients receive netupitant/palonosetron hydrochloride PO on day 1. Within 30 minutes prior to chemotherapy, patients also receive dexamethasone PO on days 1-4. Patients also receive placebo PO with chemotherapy Q8H on days 1-4.
Dexamethasone: Given PO
Laboratory Biomarker Analysis: Correlative studies
Netupitant/Palonosetron Hydrochloride: Given PO
Placebo: Given PO
Quality-of-Life Assessment: Ancillary studies | 91 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive prochlorperazine PO Q8H and placebo PO with chemotherapy on days 1-4.
Dexamethasone: Given PO
Laboratory Biomarker Analysis: Correlative studies
Netupitant/Palonosetron Hydrochloride: Given PO
Placebo: Given PO
Prochlorperazine: Given PO
Quality-of-Life Assessment: Ancillary studies | 110 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive olanzapine PO and placebo PO Q8H with chemotherapy on days 1-4.
Dexamethasone: Given PO
Laboratory Biomarker Analysis: Correlative studies
Netupitant/Palonosetron Hydrochloride: Given PO
Olanzapine: Given PO
Placebo: Given PO
Quality-of-Life Assessment: Ancillary studies | 109 |
| Total | 310 |
Baseline characteristics
| Characteristic | Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Total |
|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 11.3 | 50.0 years STANDARD_DEVIATION 11.5 | 50.2 years STANDARD_DEVIATION 11.8 | 50.7 years STANDARD_DEVIATION 11.5 |
| Education College or Grad School | 20 Participants | 27 Participants | 23 Participants | 70 Participants |
| Education High School or Less | 71 Participants | 83 Participants | 86 Participants | 240 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 102 Participants | 99 Participants | 280 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 5 Participants | 17 Participants |
| Marital Status Divorced | 8 Participants | 7 Participants | 3 Participants | 18 Participants |
| Marital Status Married / Long Term | 66 Participants | 86 Participants | 81 Participants | 233 Participants |
| Marital Status Separated | 4 Participants | 2 Participants | 6 Participants | 12 Participants |
| Marital Status Single | 10 Participants | 11 Participants | 15 Participants | 36 Participants |
| Marital Status Widowed | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 6 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 14 Participants | 15 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 75 Participants | 86 Participants | 84 Participants | 245 Participants |
| Sex: Female, Male Female | 91 Participants | 110 Participants | 109 Participants | 310 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 91 | 0 / 110 | 0 / 109 |
| other Total, other adverse events | 10 / 91 | 19 / 110 | 14 / 109 |
| serious Total, serious adverse events | 1 / 91 | 3 / 110 | 3 / 109 |
Outcome results
Primary
Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm)
Will be measured on a 7-point scale (1: not at all nauseated, 4: moderately nauseated, 7: extremely nauseated). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night).
Time frame: Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 4.51 units on a scale | Standard Error 0.155 |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 3.22 units on a scale | Standard Error 0.164 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 2.68 units on a scale | Standard Error 0.147 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 4.70 units on a scale | Standard Error 0.141 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 2.37 units on a scale | Standard Error 0.152 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 4.93 units on a scale | Standard Error 0.141 |
p-value: 0.008ANOVA
p-value: <0.001ANOVA
Primary
Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm)
Will be measured on a 7-point scale (1: not at all nauseated, 4: moderately nauseated, 7: extremely nauseated). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night).
Time frame: Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 2.40 units on a scale | Standard Error 0.12 |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 1.90 units on a scale | Standard Error 0.101 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 2.58 units on a scale | Standard Error 0.109 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 1.62 units on a scale | Standard Error 0.09 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 1 | 2.50 units on a scale | Standard Error 0.109 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm) | Cycle 2 | 1.45 units on a scale | Standard Error 0.093 |
p-value: 0.01ANOVA
p-value: 0.001ANOVA
Secondary
The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared.
Will be measured on a 7-point scale anchored by 1:not at all nauseated and 7:extremely nauseated. Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 and 16 assessment points for Cycle 2. This will be assessed by estimating the contrast D = (3 - 1) - (2 - 1), where 3 is the Arm 3 mean, 2 is the Arm 2 mean, and 1 is the Control mean.
Time frame: Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 1 | 4.51 units on a scale | Standard Error 0.155 |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 2 | 3.22 units on a scale | Standard Error 0.164 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 1 | 4.70 units on a scale | Standard Error 0.141 |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 2 | 2.68 units on a scale | Standard Error 0.147 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 1 | 4.93 units on a scale | Standard Error 0.141 |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by (1:Not at All Nauseated and 7:Extremely Nauseated). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared. | Cycle 2 | 2.37 units on a scale | Standard Error 0.152 |
Comparison: Secondary Aim 1 is to determine if olanzapine is more effective than prochlorperazine in controlling nausea at Cycle 2 in participants who experienced CINV at Cycle 1 when used in combination with netupitant, palonosetron and dexamethasone.~This will be assessed by estimating the contrast D = (3 - 1) - (2 - 1), where 3 is the Arm 3 mean, 2 is the Arm 2 mean, and 1 is the Control mean, and testing whether D = 0 versus the one-sided alternative hypothesis that D \> 0.p-value: 0.019t-test, 2 sided
Secondary
Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1.
The response variable will be Any VOMITING (yes/no) after Cycle 2 Chemotherapy, treatment arm as the main factor, and Any Vomiting after Cycle 1 as a covariate. Estimation will be performed using maximum likelihood assuming a binomial distribution and logit link. The same group of contrasts described in the Primary Aim analysis will be estimated and tested, with a significance level of 0.025 to adjust for multiple tests.
Time frame: Vomiting measured at Cycle 1 Chemotherapy (Yes/No on Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (Yes/No on Days 1,2,3,4)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | No | 79 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Yes | 7 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Unknown | 5 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | No | 103 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Yes | 4 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Unknown | 3 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Yes | 2 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | Unknown | 9 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1. | No | 98 Participants |
p-value: 0.38697.5% CI: [0.65, 2.66]Regression, Logistic
p-value: 0.03697.5% CI: [0.02, 1.13]Regression, Logistic
Other Pre-specified
Emetogenic Potential
Emetogenic Potential: The percentage of risk of vomiting based on given chemotherapy agents. Reference: https://pubmed.ncbi.nlm.nih.gov/38129530/
Time frame: Cycle 2 Chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Emetogenic Potential | Unknown | 4 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Emetogenic Potential | High ( >=90 % risk of vomiting ) | 54 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Emetogenic Potential | Moderate ( 30 - 90 % risk of vomiting ) | 33 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Emetogenic Potential | Unknown | 2 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Emetogenic Potential | Moderate ( 30 - 90 % risk of vomiting ) | 40 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Emetogenic Potential | High ( >=90 % risk of vomiting ) | 68 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Emetogenic Potential | High ( >=90 % risk of vomiting ) | 55 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Emetogenic Potential | Moderate ( 30 - 90 % risk of vomiting ) | 52 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Emetogenic Potential | Unknown | 2 Participants |
Other Pre-specified
Regimens: Chemotherapy Regimens at Cycle 2
Grouping of Chemotherapy Regimens at Cycle 2
Time frame: Cycle 2 Chemotherapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Regimens: Chemotherapy Regimens at Cycle 2 | Others | 0 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Regimens: Chemotherapy Regimens at Cycle 2 | Platinum based | 14 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Regimens: Chemotherapy Regimens at Cycle 2 | Anthracycline based | 54 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Regimens: Chemotherapy Regimens at Cycle 2 | Taxane based | 19 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Regimens: Chemotherapy Regimens at Cycle 2 | Unknown | 4 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Platinum based | 16 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Anthracycline based | 68 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Taxane based | 22 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Others | 2 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Unknown | 2 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Unknown | 2 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Others | 3 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Anthracycline based | 55 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Platinum based | 27 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Regimens: Chemotherapy Regimens at Cycle 2 | Taxane based | 22 Participants |
Other Pre-specified
Vomiting at Cycle 1 of Chemotherapy
Record of any vomiting (Yes/No) during Cycle 1 of Chemotherapy on Days 1, 2, 3, 4
Time frame: Cycle 1 Chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting at Cycle 1 of Chemotherapy | No | 79 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting at Cycle 1 of Chemotherapy | Yes | 12 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting at Cycle 1 of Chemotherapy | No | 92 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting at Cycle 1 of Chemotherapy | Yes | 18 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting at Cycle 1 of Chemotherapy | Yes | 19 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting at Cycle 1 of Chemotherapy | No | 90 Participants |
Other Pre-specified
Vomiting at Cycle 2 of Chemotherapy
Record of any vomiting (Yes/No) during Cycle 2 of Chemotherapy on Days 1, 2, 3, 4
Time frame: Cycle 2 Chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting at Cycle 2 of Chemotherapy | No | 79 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting at Cycle 2 of Chemotherapy | Yes | 7 Participants |
| Group I (Netupitant/Palonosetron Hydrochloride, Dexamethasone | Vomiting at Cycle 2 of Chemotherapy | Unknown | 5 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | No | 103 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | Yes | 4 Participants |
| Group II (Net/Pal Hydro, Dexa, Prochlorperazine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | Unknown | 3 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | Yes | 2 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | Unknown | 9 Participants |
| Group III (Net/Pal Hydro, Dexa, Olanzapine, Placebo) | Vomiting at Cycle 2 of Chemotherapy | No | 98 Participants |