Chemotherapy-Induced Nausea and Vomiting
Conditions
Brief summary
PALO-15-17 is a clinical study assessing efficacy and safety of a single dose of palonosetron 0.25 mg administered as a 30-minute IV infusion compared to palonosetron 0.25 mg administered as a 30-second IV bolus (Aloxi, an antiemetic drug), both given with oral dexamethasone. The objective of the study is to demonstrate that infused IV palonosetron 0.25 mg is as effective as (non-inferior to) injected palonosetron IV 0.25 mg to prevent nausea and vomiting induced by highly emetogenic cancer chemotherapy in the 0-24 hours after administration of a single cycle of highly emetogenic chemotherapy
Interventions
DRUGPalonosetron
DRUGDexamethasone
Sponsors
PSI CRO
Helsinn Healthcare SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Histologically or cytologically confirmed solid tumor malignancy. * Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted. * Scheduled to receive first course of one of the following reference HEC, alone or in combination with other chemotherapeutic agents on Day 1: * cisplatin administered as a single IV dose of ≥ 70 mg/m2 * cyclophosphamide ≥1500 mg/m2 * carmustine (BCNU) \>250 mg/m2 * dacarbazine (DTIC) * mechloretamine (nitrogen mustard) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 . * If a patient is female, she shall be of non-childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. * Hematologic and metabolic status adequate for receiving an highly emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance) * Able to read, understand, follow the study procedure and complete patient diary.
Exclusion criteria
* Lactating woman. * Current use of illicit drugs or current evidence of alcohol abuse. * Scheduled to receive moderately emetogenic chemotherapy or highly emetogenic chemotherapy from Day 2 to Day 5. * Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference HEC administration on Day 1 or between Days 1 to 5. * Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of the reference HEC administration on Day 1. * Symptomatic primary or metastatic CNS malignancy. * Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any illness or medical conditions (other than malignancy) that, in the opinion of the Investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting) or pose unwarranted risks in administering the study drugs to the patient. * Known hypersensitivity or contraindication to 5-HT3 receptor antagonists * Known contraindication to the IV administration of 50 mL 5% glucose solution. * Participation in a previous clinical trial involving palonosetron. * Any investigational drugs (other than those given in this study) taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug during the present study. * Systemic corticosteroid therapy at any dose within 72 hours prior to the start of the reference HEC administration on Day 1. However, topical and inhaled corticosteroids are permitted. * Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy. * Any medication with known or potential antiemetic activity within 24 hours prior to the start of the reference HEC administration on Day 1, including but not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists * Concurrent medical condition that would preclude administration of dexamethasone for 4 days such as systemic fungal infection or uncontrolled diabetes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase | 0-24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase | 0-120 hours |
| Percentage of Patients With no Emetic Episodes in the Acute Phase | 0-24 hours |
| Percentage of Patients With no Emetic Episodes in the Delayed Phase | >24-120 hours |
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase | >24-120 hours |
| Percentage of Patients With no Rescue Medication in the Acute Phase | 0-24 hours |
| Percentage of Patients With no Rescue Medication in the Delayed Phase | >24-120 hours |
| Percentage of Patients With no Rescue Medication in the Overall Phase | 0-120 hours |
| Percentage of Patients With no Emetic Episodes in the Overall Phase | 0-120 hours |
Countries
Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Greece, Hungary, Lithuania, Romania, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone Intravenous palonosetron (Aloxi 0.25 mg solution for injection) as an infusion with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4.
Palonosetron
Dexamethasone | 225 |
| I.V. Palonosetron Bolus Plus Dexamethasone Intravenous palonosetron (Aloxi 0.25 mg solution for injection) as a bolus with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4.
Palonosetron
Dexamethasone | 215 |
| Total | 440 |
Baseline characteristics
| Characteristic | I.V. Palonosetron Bolus Plus Dexamethasone | Total | I.V. Palonosetron Infusion Plus Dexamethasone |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 8.5 | 59.4 years STANDARD_DEVIATION 8.6 | 59.9 years STANDARD_DEVIATION 8.7 |
| Alcohol consumption None | 145 Participants | 305 Participants | 160 Participants |
| Alcohol consumption Occasional | 67 Participants | 125 Participants | 58 Participants |
| Alcohol consumption Regular | 3 Participants | 10 Participants | 7 Participants |
| ECOG Performance Status Grade 0 | 109 Participants | 206 Participants | 97 Participants |
| ECOG Performance Status Grade 1 | 100 Participants | 220 Participants | 120 Participants |
| ECOG Performance Status Grade 2 | 6 Participants | 14 Participants | 8 Participants |
| 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 | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 215 Participants | 440 Participants | 225 Participants |
| Sex: Female, Male Female | 71 Participants | 145 Participants | 74 Participants |
| Sex: Female, Male Male | 144 Participants | 295 Participants | 151 Participants |
| Tobacco consumption Ex-smoker | 70 Participants | 151 Participants | 81 Participants |
| Tobacco consumption non-smoker | 77 Participants | 158 Participants | 81 Participants |
| Tobacco consumption Occasional | 2 Participants | 5 Participants | 3 Participants |
| Tobacco consumption Regular | 66 Participants | 126 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 225 | 0 / 215 |
| other Total, other adverse events | 14 / 225 | 22 / 215 |
| serious Total, serious adverse events | 15 / 225 | 12 / 215 |
Outcome results
Primary
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase
Time frame: 0-24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase | 186 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase | 186 Participants |
Secondary
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase
Time frame: >24-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase | 170 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase | 165 Participants |
Secondary
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase
Time frame: 0-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase | 150 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase | 156 Participants |
Secondary
Percentage of Patients With no Emetic Episodes in the Acute Phase
Time frame: 0-24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Acute Phase | 186 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Acute Phase | 190 Participants |
Secondary
Percentage of Patients With no Emetic Episodes in the Delayed Phase
Time frame: >24-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Delayed Phase | 176 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Delayed Phase | 168 Participants |
Secondary
Percentage of Patients With no Emetic Episodes in the Overall Phase
Time frame: 0-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Overall Phase | 155 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Emetic Episodes in the Overall Phase | 160 Participants |
Secondary
Percentage of Patients With no Rescue Medication in the Acute Phase
Time frame: 0-24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Acute Phase | 200 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Acute Phase | 195 Participants |
Secondary
Percentage of Patients With no Rescue Medication in the Delayed Phase
Time frame: >24-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Delayed Phase | 183 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Delayed Phase | 176 Participants |
Secondary
Percentage of Patients With no Rescue Medication in the Overall Phase
Time frame: 0-120 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| I.V. Palonosetron Infusion Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Overall Phase | 173 Participants |
| I.V. Palonosetron Bolus Plus Dexamethasone | Percentage of Patients With no Rescue Medication in the Overall Phase | 169 Participants |