Chemotherapy-Induced Nausea and Vomiting
Conditions
Brief summary
PALO-10-01 is a clinical study assessing efficacy and safety of a single oral dose of palonosetron compared to a single intravenous dose of palonosetron (Aloxi, an antiemetic drug), both given with oral dexamethasone. The objective of the study is to demonstrate that oral palonosetron 0.50 mg is as effective as (non-inferior to) 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
DRUGOral palonosetron
DRUGI.V. palonosetron
DRUGDexamethasone
Sponsors
Parexel
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
* Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted. * Diagnosed with a malignant solid tumor and scheduled to receive first course of cytotoxic chemotherapy with cisplatin administered as a single I.V. dose of equal or more than 70 mg/m2 over 1-4 hours on study Day 1, either alone or in combination with other chemotherapeutic agents. * If scheduled to receive combination regimens, non-cisplatin agents of moderate to high emetogenic potential are allowed and they must be administered following the cisplatin infusion and completed no more than 6 hours after the initiation of cisplatin infusion. * If scheduled to receive chemotherapy agents of minimal to low emetogenic potential, they are to be given on Day 1 following cisplatin or on any subsequent study day. * ECOG Performance Status of 0, 1, or 2 * Female patients of either non-childbearing potential or child-bearing potential with a commitment to use contraceptive methods throughout the clinical trial * Hematologic and metabolic status adequate for receiving a highly emetogenic cisplatin-based regimen based on laboratory criteria (Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance) * If a patient has a known hepatic or renal impairment, he/she may be enrolled in this study at the discretion of the Investigator. * If a patient has a known history or predisposition to cardiac conduction interval abnormalities he/she may be enrolled in this study at the discretion of the Investigator.
Exclusion criteria
* If female, pregnant or lactating. * Current use of illicit drugs or current evidence of alcohol abuse. * Scheduled to receive moderately emetogenic chemotherapy (MEC) or HEC from Day 2 to Day 5 following cisplatin administration. * Received or is scheduled to receive radiation therapy to the abdomen, or the pelvis within 1 week prior to Day 1 or between Days 1 to 5. * Any vomiting, retching, or mild nausea within 24 hours prior to Day 1. * Symptomatic primary or metastatic CNS malignancy. * Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any uncontrolled 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, CINV) or pose unwarranted risks in administering the study drugs to the patient. * Known hypersensitivity or contraindication to 5-HT3 receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron) or dexamethasone. * Participation in a 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 study. * Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1. However topical and inhaled corticosteroids with a steroid dose of £ 10 mg of prednisone daily or its equivalent 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 Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication | 0-24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients With no Emesis | 0-24 hours |
| Percentage of Patients With no Rescue Medication | 0-24 hours |
Countries
Argentina, Bulgaria, Croatia, Germany, Hungary, India, Italy, Poland, Romania, Russia, Ukraine, United States
Participant flow
Pre-assignment details
A total of 743 patients were randomized (ITT population), 739 received study medications (oral or I.V. palonosetron plus dexamethasone, safety population), 738 received study medications (oral or I.V. palonosetron plus dexamethasone, safety population) and chemotherapy (FAS population)
Participants by arm
| Arm | Count |
|---|---|
| Oral Palonosteron Plus Dexamethasone Oral palonosetron (Aloxi 0.50 mg softgel capsule) with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4.
Oral palonosetron
Dexamethasone | 370 |
| I.V. Palonosetron Plus Dexamethasone Intravenous palonosetron (Aloxi 0.25 mg solution for injection) with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4.
I.V. palonosetron
Dexamethasone | 369 |
| Total | 739 |
Baseline characteristics
| Characteristic | Oral Palonosteron Plus Dexamethasone | I.V. Palonosetron Plus Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 9.41 | 57.7 years STANDARD_DEVIATION 9.92 | 57.9 years STANDARD_DEVIATION 9.66 |
| Race/Ethnicity, Customized Asian | 49 participants | 47 participants | 96 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 321 participants | 320 participants | 641 participants |
| Sex: Female, Male Female | 151 Participants | 152 Participants | 303 Participants |
| Sex: Female, Male Male | 219 Participants | 217 Participants | 436 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 168 / 370 | 171 / 369 |
| serious Total, serious adverse events | 36 / 370 | 36 / 369 |
Outcome results
Primary
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication
Time frame: 0-24 hours
Population: Full Analysis Set i.e. patients receiving study drugs and chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Palonosteron Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication | 89.4 percentage of responders |
| I.V. Palonosetron Plus Dexamethasone | Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication | 86.2 percentage of responders |
99% CI: [-2.74, 9.17]
Secondary
Percentage of Patients With no Emesis
Time frame: 0-24 hours
Population: FAS i.e. patients receiving study drugs and chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Palonosteron Plus Dexamethasone | Percentage of Patients With no Emesis | 90.2 percentage of responders |
| I.V. Palonosetron Plus Dexamethasone | Percentage of Patients With no Emesis | 86.7 percentage of responders |
Secondary
Percentage of Patients With no Rescue Medication
Time frame: 0-24 hours
Population: FAS i.e. patients receiving study drugs and chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Palonosteron Plus Dexamethasone | Percentage of Patients With no Rescue Medication | 94.6 percentage of responders |
| I.V. Palonosetron Plus Dexamethasone | Percentage of Patients With no Rescue Medication | 93.2 percentage of responders |