Malignant Neoplasm
Conditions
Keywords
ondansetron, palonosetron, emetogenic chemotherapy, HEC
Brief summary
Palonosetron is different from ondansetron because it stays in the body longer and may prevent nausea and vomiting for a longer period of time than ondansetron. It is standard practice to use dexamethasone and aprepitant with either ondansetron or palonosetron to prevent nausea and vomiting caused by highly emetogenic chemotherapy. Although these combinations are commonly used, they have never been compared to each other. The purpose of this study is to record the amount of nausea and vomiting, and the amount of rescue medication that is used with these two different anti-emetic regimens
Detailed description
PRIMARY OBJECTIVES: I. The goal of this study is to evaluate the overall complete response rate (CR, no emesis and no use of rescue medication from 0 to 120 hours after chemotherapy) of two different antiemetic regimens (palonosetron + aprepitant + dexamethasone and ondansetron + aprepitant + dexamethasone) for patients undergoing the first cycle of highly emetogenic chemotherapy (HEC). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive palonosetron hydrochloride intravenously (IV) 30 minutes prior to chemotherapy on day 1, aprepitant orally (PO) 60 minutes prior to chemotherapy on days 1-3, and dexamethasone PO 30 minutes prior to chemotherapy on days 1-4. ARM II: Patients receive ondansetron PO 30 minutes prior to chemotherapy on day 1 and aprepitant and dexamethasone as in Arm I. After completion of study treatment, patients are followed up for 7 days.
Interventions
DRUGaprepitant
Given by mouth
Given IV(intervenous infusion)
DRUGondansetron
Given PO
DRUGdexamethasone
Given PO
Sponsors
Ohio State University Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 88 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed malignancy * Chemotherapy naive or treated with only low or minimally emetogenic chemotherapy in the past (as defined by the National Comprehensive Cancer Network version \[v\].2.201 Antiemetic Guidelines) * Scheduled to receive the first dose of their first cycle of HEC * Patients receiving multi-day chemotherapy, the HEC portion must be on day 1 and the remaining days of chemotherapy must be minimally emetogenic (i.e. fluorouracil) * Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0-2 * Able to provide informed consent * Able to read and write in English or have someone that can that can translate to them and record their diary entries * Able to take oral medications * Patients are allowed to participate in a concurrent clinical trial, if the other trial: * Does not mandate an antiemetic regimen that interferes with this study * Allows antiemetic administration at the physician's discretion * Does not prohibit the patient from participating in this study * Patients must be willing to participate with daily diary entries for 5 days following chemotherapy, and agree to have a 5 minute follow-up call on day 2 or 3 and day 5, 6 or 7
Exclusion criteria
* Has stage IV (metastatic) disease * Known hypersensitivity to ondansetron, palonosetron, aprepitant, or dexamethasone * Have received or will receive agents that are strong cytochrome P450 3A4 (CYP450 3A4) inducers and/or inhibitors and known to cause clinically relevant drug interactions within one week prior to study treatment and continuing through day 5; any vomiting or retching within 24 hours before administration of chemotherapy * Grade 2 nausea or greater, according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) within 24 hours before administration of chemotherapy * Received an antiemetic within 24 hours before study drug administration, excluding the use of benzodiazepines * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2.5 times upper limit of normal * Total bilirubin \> 1.5 times upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall CR(Complete Response)After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication | Up to 120 hours after completion of chemotherapy | We will use exact binomial methods to estimate proportions and their associated 95% confidence intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delayed CR (Complete Response) | 24-120 hours after chemotherapy | After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication From Time 24to 120 Hours. |
| Percentage of Patients Who Experienced Grade 1, 2 or 3 Nausea From Time 0 to 120 Hours | Time 0 to 120 hours | The percentage of patients who experienced grade 1, 2 or 3 nausea from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE (Common Toxicity Criteria for Adverse Effects)version 4.0 Nausea Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated. |
| Acute CR (Complete Response) | 0-24 hours after chemotherapy | After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication from time 0 to 24 hours. |
| Use of Rescue Medication for Each Treatment Arm | From time 0 to 120 hours | — |
| Percentage of Patients Who Experienced Grade 1, 2 or 3 Vomiting From Time 0 to 120 Hours | From time 0 to 120 hours | The percentage of patients who experienced grade 1, 2 or 3 vomiting from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE v 4.0 vomiting Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated. |
| Visual Analog Scale (VAS) Scores | Up to 7 days after completion of study treatment | — |
Countries
United States
Participant flow
Recruitment details
Patients were screened for eligibility during routine clinic visits by a physician, nurse practitioner or pharmacist involved in their care.
Pre-assignment details
Patients were stratified based upon their chemotherapy regimen (cisplatin versus noncisplatin containing) and then randomized to the ondansetron or palonosetron group.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Palonosetron 0.25 mg day 1; aprepitant 125 mg day 1, 80 mg day 2-3; dexamethasone 12 mg day 1, 8 mg day 2-4 | 20 |
| Arm B Ondansetron 24 mg day 1; aprepitant 125 mg day 1, 80 mg day 2-3; dexamethasone 12 mg day 1, 8 mg day 2-4 | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 17 Participants | 32 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 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 | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 |
Outcome results
Primary
Overall CR(Complete Response)After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication
We will use exact binomial methods to estimate proportions and their associated 95% confidence intervals.
Time frame: Up to 120 hours after completion of chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Overall CR(Complete Response)After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication | 65 percentage of patients |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Overall CR(Complete Response)After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication | 40 percentage of patients |
Secondary
Acute CR (Complete Response)
After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication from time 0 to 24 hours.
Time frame: 0-24 hours after chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Acute CR (Complete Response) | 75 percentage of particpants |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Acute CR (Complete Response) | 55 percentage of particpants |
Secondary
Delayed CR (Complete Response)
After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication From Time 24to 120 Hours.
Time frame: 24-120 hours after chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Delayed CR (Complete Response) | 65 percentage of participants |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Delayed CR (Complete Response) | 45 percentage of participants |
Secondary
Percentage of Patients Who Experienced Grade 1, 2 or 3 Nausea From Time 0 to 120 Hours
The percentage of patients who experienced grade 1, 2 or 3 nausea from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE (Common Toxicity Criteria for Adverse Effects)version 4.0 Nausea Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated.
Time frame: Time 0 to 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Percentage of Patients Who Experienced Grade 1, 2 or 3 Nausea From Time 0 to 120 Hours | 55 percentage of participants |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Percentage of Patients Who Experienced Grade 1, 2 or 3 Nausea From Time 0 to 120 Hours | 65 percentage of participants |
Secondary
Percentage of Patients Who Experienced Grade 1, 2 or 3 Vomiting From Time 0 to 120 Hours
The percentage of patients who experienced grade 1, 2 or 3 vomiting from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE v 4.0 vomiting Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated.
Time frame: From time 0 to 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Percentage of Patients Who Experienced Grade 1, 2 or 3 Vomiting From Time 0 to 120 Hours | 5 percentage of participants |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Percentage of Patients Who Experienced Grade 1, 2 or 3 Vomiting From Time 0 to 120 Hours | 15 percentage of participants |
Secondary
Use of Rescue Medication for Each Treatment Arm
Time frame: From time 0 to 120 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Palonosetron 0.25 mg IV on Day 1) | Use of Rescue Medication for Each Treatment Arm | 35 percentage of participants |
| Arm B (Ondansetron 24 mg Oral on Day 1) | Use of Rescue Medication for Each Treatment Arm | 55 percentage of participants |
Secondary
Visual Analog Scale (VAS) Scores
Time frame: Up to 7 days after completion of study treatment
Population: VAS Scores were not collected