An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Helsinn Healthcare SA
ClinicalTrials.gov Identifier:
NCT01339260
First received: April 19, 2011
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

NETU-08-18 is a clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.


Condition Intervention Phase
Chemotherapy-Induced Nausea and Vomiting
Drug: Netupitant and Palonosetron
Drug: Palonosetron
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase III Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of the Efficacy and Safety of Oral Netupitant Administered in Combination With Palonosetron and Dexamethasone Compared to Oral Palonosetron and Dexamethasone for the Prevention of Nausea and Vomiting in Cancer Patients Receiving Moderately Emetogenic Chemotherapy

Resource links provided by NLM:


Further study details as provided by Helsinn Healthcare SA:

Primary Outcome Measures:
  • Proportion of patients with complete response (CR) defined as no emesis, no rescue medication, at cycle 1 [ Time Frame: 25-120 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with complete response (CR) defined as no emesis, no rescue medication at cycle 1 [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
  • Proportion of patients with complete response (CR) defined as no emesis, no rescue medication, at cycle 1 [ Time Frame: 0-120 hours ] [ Designated as safety issue: No ]

Enrollment: 1455
Study Start Date: April 2011
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Netupitant and Palonosetron plus dexamethasone
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone, both given on Day 1, prior to each scheduled chemotherapy cycle
Drug: Netupitant and Palonosetron Drug: Dexamethasone
Active Comparator: Palonosetron plus dexamethasone
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone both given on Day 1, prior to each scheduled chemotherapy cycle
Drug: Palonosetron Drug: Dexamethasone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
  • Scheduled to receive first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy (MEC) regimen for the treatment of a solid malignant tumor: cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. doxorubicin (more or equal to 40 mg/m2) or cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. epirubicin (more or equal to 60 mg/m2).
  • If scheduled to receive chemotherapy agents of minimal to low emetogenic potential they could be given on any 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 moderately emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)

The following inclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

  • Participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator Satisfactory study compliance in the preceding cycle of chemotherapy and related study procedures.
  • Scheduled to receive the same chemotherapy regimen as cycle 1
  • Adequate hematologic and metabolic status as defined for cycle 1

Exclusion Criteria:

  • If female, pregnant or lactating.
  • Current use of illicit drugs or current evidence of alcohol abuse.
  • Scheduled to receive any highly emetogenic chemotherapy (HEC) from Day 1 to Day 5 or moderately emetogenic chemotherapy (MEC) from Day 2 to Day 5 following the allowed MEC regimen.
  • 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 in cycle 1.
  • 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 condition (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 or dexamethasone.
  • Previously received an NK1 receptor antagonist
  • Participation in a clinical trial involving oral netupitant administered in combination with palonosetron.
  • Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 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 of cycle 1.
  • 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 of cycle 1
  • Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1 week prior to Day 1.
  • Scheduled to receive any of the following CYP3A4 substrates: terfenadine, cisapride, astemizole, pimozide.
  • Scheduled to receive any CYP3A4 inducer or its intake within 4 weeks prior to Day 1.
  • History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
  • History of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
  • Severe cardiovascular diseases, including myocardial infarction within 3 months prior to Day 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) NYHA class III-IV, and severe uncontrolled arterial hypertension.
  • Any illness or condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
  • Concurrent medical condition that would preclude administration of dexamethasone such as systemic fungal infection or uncontrolled diabetes.

The following exclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

  • If female, pregnant or lactating
  • Active infection or uncontrolled disease except for malignancy.
  • Started any of the restricted medications.
  • Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01339260

  Show 172 Study Locations
Sponsors and Collaborators
Helsinn Healthcare SA
Parexel
  More Information

No publications provided

Responsible Party: Helsinn Healthcare SA
ClinicalTrials.gov Identifier: NCT01339260     History of Changes
Other Study ID Numbers: NETU-08-18
Study First Received: April 19, 2011
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Belarus: Ministry of Health
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Hungary: National Institute of Pharmacy
Germany: Federal Institute for Drugs and Medical Devices
Romania: National Medicines Agency
Romania: Ethics Committee
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
Croatia: Agency for Medicinal Product and Medical Devices
Croatia: Ethics Committee
Poland: National Institute of Medicines
Poland: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Ukraine: Ethics Committee
Ukraine: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Mexico: Ministry of Health
Mexico: Ethics Committee
India: Central Drugs Standard Control Organization
India: Institutional Review Board

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Palonosetron
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on April 23, 2014