A single-dose study to asses the efficacy and safety of palonosetron administered as 30-minute infusion compared to palonosetron administered as a 30-second injection for preventing chemotherapy-induced nausea and vomiting in cancer patients.

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2015-001747-37-HU
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: Helsinn Healthcare SA
• Public title: A single-dose study to asses the efficacy and safety of palonosetron administered as 30-minute infusion compared to palonosetron administered as a 30-second injection for preventing chemotherapy-induced nausea and vomiting in cancer patients.
• Scientific title: A phase 3, single-dose, multicenter, randomized, double-blind, parallel group study to assess the efficacy and safety 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 for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving highly emetogenic chemotherapy.
• Date of first enrolment: 28/07/2015
• Target sample size: 440
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001747-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double-dummy If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Aloxi 30-second i.v. bolus Number of treatment arms in the trial: 2

Countries of recruitment

Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Greece, Hungary, Lithuania, Romania, Russian Federation

Contacts

• Name: Medical Monitor
• Affiliation: PSI CRO AG

• Name: Medical Monitor
• Affiliation: PSI CRO AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent.
2. Male or female patient = 18 years of age.
3. Histologically or cytologically confirmed solid tumor malignancy.
4. Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.
5. 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) > 250mg/m2
- dacarbazine (DTIC)
- mechloretamine (nitrogen mustard)
The administration of the reference HEC should not extend beyond 4 hours on study Day 1.
* on Day 1, additional chemotherapeutic agents have to be administered after the start of the reference HEC administration and their administration must be completed no more than 6 hours after the start of reference HEC infusion. Low, minimally or not emetogenic chemotherapies can be administered at any time from Day 2 onwards.
6. ECOG Performance Status of 0, 1, or 2.
7. Non-childbearing female patient or female patient of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test.
8. Hematologic and metabolic status adequate for receiving a HEC regimen and fulfillment of the following criteria:
a) Total Neutrophils = 1500/mm3 (Standard units: = 1.5 x 10^9/L)
b) Platelets = 100,000/mm3 (Standard units: = 100.0 x 10^9/L)
c) Bilirubin = 1.5 x Upper Limit of Normal (ULN)
d) Liver enzymes:
i. Without known liver metastases, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 x ULN
ii. With known liver metastases, AST and ALT = 5.0 x ULN
e) Serum Creatinine = 1.5 mg/dL (Standard units: = 132.6 µMOL/L) or Creatinine Clearance = 60 mL/min.
9. If a patient has a known hepatic or renal impairment, he/she may be enrolled in this study at the discretion of the Investigator, provided the inclusion criterion #8 items d) and e) are satisfied.
10. If a patient has a known history or predisposition to cardiac conduction interval abnormalities, including QTc, he/she may be enrolled in this study at the discretion of the Investigator.
11. Able to read, understand, follow the study procedure and complete the patient diary.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
1. Lactating woman.
2. Current use of illicit drugs or current evidence of alcohol abuse.
3. Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day 5.
4. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of reference HEC administration on Day 1 or between Days 1 to 5.
5. Any vomiting, retching, or nausea (grade = 1 as defined by National Cancer Institute) within 24 hours prior to the start of reference HEC administration on Day 1.
6. Symptomatic primary or metastatic CNS malignancy.
7. 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 [CINV]) or pose unwarranted risks in administering the study drugs to the patient.
8. Known hypersensitivity or contraindication to 5-HT3 receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron) or dexamethasone.
9. Known contraindication to the IV administration of 50 mL 5% glucose solution.
10. Participation in a previous clinical trial involving palonosetron.
11. 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.
12. Systemic corticosteroid therapy at any dose within 72hours prior to the start of reference HEC administration on Day 1. However, topical and inhaled corticosteroids are permitted.
13. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
14. Any medication with known or potential antiemetic activity within 24 hours prior to the start of reference HEC administration on Day 1, including:
• 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron)
• NK-1 receptor antagonists (e.g., aprepitant or any other new drug of this class)
• benzamides (e.g., metoclopramide, alizapride)
• phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine)
• benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to Day 1).
• butyrophenones (e.g., haloperidol, droperidol)
• anticholinergics (e.g., scopolamine, with the exception of inhaled anticholinergics for respiratory disorders, e.g., ipratropium bromide)
• antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine, chlorpheniramine)
• domperidone
• mirtazapine
• olanzapine
• prescribed cannabinoides (e.g., tetrahydrocannabinol or nabilone)
• Over The Counter (OTC) antiemetics, OTC cold or OTC allergy medications.
15. Concurrent medical condition that would preclude administration of dexamethasone for 4 days such as systemic fungal infection or uncontrolled diabetes.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

nausea and vomiting in cancer patients receiving highly emetogenic therapy
MedDRA version: 18.0 Level: LLT Classification code 10036899 Term: Prophylaxis against chemotherapy induced vomiting System Organ Class: 100000004865

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Aloxi
Product Name: Aloxi
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PALONOSETRON
CAS Number: 135729-62-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous drip use (Noncurrent)

Trade Name: Aloxi
Product Name: Aloxi
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PALONOSETRON
CAS Number: 135729-62-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous bolus use (Noncurrent)

Primary Outcome(s)

Secondary Objective: To evaluate the safety of a single intravenous dose of palonosetron 0.25 mg administered as a 30-minute infusion with oral dexamethasone for the prevention of chemotherapy induced nausea and vomiting.

Timepoint(s) of evaluation of this end point: Acute phase (time interval 0 to 24 hours after the start of reference HEC)

Main Objective: To demonstrate the non-inferiority of a single intravenous dose of palonosetron 0.25 mg administered as a 30-minute infusion with oral dexamethasone versus a single intravenous dose of palonosetron 0.25 mg administered as a 30-second bolus with oral dexamethasone, in terms of proportion of patients with complete response in the acute phase (0-24 hours after start of reference HEC)

Primary end point(s): The proportion of patients with Complete Response (CR) (defined as no emetic episodes and no rescue medication) in the acute phase.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Acute phase (time interval 0 to 24 hours after the start of reference HEC), delayed phase (>24 to 120 hours after the start of reference HEC) and overall phase (0 to 120 hours after the start of reference HEC).

Secondary end point(s): Efficacy:
• the proportion of patients with CR during the delayed and overall phases;
• the proportion of patients with no emetic episodes during the acute, delayed and overall phases;
• the proportion of patients with no rescue medication during the acute, delayed and overall phases.

Safety:
The following safety assessments will be obtained: physical examination (PE), vital signs, 12-lead electrocardiogram (ECG), laboratory tests (hematology, blood chemistry, urinalysis), and adverse events (AEs) assessment.

Secondary ID(s)

PALO-15-17

Source(s) of Monetary Support

Helsinn Healthcare SA