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A 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:
NCT01376297
First received: June 16, 2011
Last updated: November 6, 2014
Last verified: November 2014
  Purpose

NETU-10-29 is a clinical study assessing safety of netupitant and palonosetron, two antiemetic drugs, both given with oral dexamethasone. The objective of the study is to evaluate if netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase III, Multicenter, Randomized, Double-blind, Unbalanced (3:1) Active Control Study to Assess the Safety and Describe the Efficacy of Netupitant and Palonosetron for the Prevention of Chemotherapy-induced Nausea and Vomiting in Repeated Chemotherapy Cycles.

Resource links provided by NLM:


Further study details as provided by Helsinn Healthcare SA:

Primary Outcome Measures:
  • Percentage of Patients With Adverse Events [ Time Frame: Participants will be followed for the duration of the chemotherapy, an expected average duration of up to 24 weeks assuming 6 chemotherapy cycles given every 4 weeks ] [ Designated as safety issue: No ]
    This was a safety study where Adverse Events is the primary outcome (defined by the current ICH Guideline for Good Clinical Practice). Patients were randomized according to a 3:1 ratio (netupitant/palonosetron:aprepitant/palonosetron). No formal comparison was planned, the presence of a control in the same patient population helped interpret any unexpected safety finding in the experimental arm.The number of patients was estimated in order to have more than 100 patients treated with the netupitant/palonosetron comination for up to at least six cycles. Based on 100 patients, if a given AE is not observed, an AE incidence of 3% or greater can be excluded with 95% confidence.


Enrollment: 413
Study Start Date: July 2011
Primary Completion Date: September 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 (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Drug: Netupitant and Palonosetron Drug: Dexamethasone
Active Comparator: Aprepitant and Palonosetron plus dexamethasone
Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle.
Drug: Aprepitant 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:

  • Signed written informed consent.
  • Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.
  • Diagnosed with a malignant tumor.
  • If scheduled to receive repeated consecutive courses of chemotherapy, a single dose of one or more of the following agents administered on Day 1 is allowed:

    • Highly emetogenic chemotherapy: any I.V. dose of cisplatin, mechlorethamine, streptozocin, cyclophosphamide more or equal to 1500 mg/m2, carmustine, dacarbazine;
    • Moderately emetogenic chemotherapy: any I.V. dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin, cyclophosphamide I.V. (less than 1500 mg/m2), cytarabine I.V. (more than 1 g/m2), azacidine, alemtuzumab, bendamustine, or clofarabine.
  • If scheduled to receive combination regimens, the most emetogenic agent is to be given as first on Day 1 and the infusion must be completed within 6 hours.
  • If scheduled to receive chemotherapy agents of minimal to low emetogenic potential, they are to be given on Day 1 following the most emetogenic agent 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 moderately emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)

Exclusion Criteria:

  • If female, lactating or pregnant
  • Current use of illicit drugs or current evidence of alcohol abuse.
  • Scheduled to receive either 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).
  • Scheduled to receive moderately or highly emetogenic chemotherapy from Day 2 to Day 5 following Day 1 chemotherapy administration.
  • Active infection or uncontrolled disease except for malignancy that may 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. Topical and inhaled corticosteroids with a steroid dose of less or equal to 10 mg of prednisone daily or its equivalent are permitted. Non-study drug dexamethasone as pre-medication in patients scheduled to receive taxanes is allowed.
  • Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
  • 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 within 3 months prior to Day 1, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure 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 for 4 days such as systemic fungal infection or uncontrolled diabetes.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01376297

  Show 75 Study Locations
Sponsors and Collaborators
Helsinn Healthcare SA
Parexel
  More Information

No publications provided

Responsible Party: Helsinn Healthcare SA
ClinicalTrials.gov Identifier: NCT01376297     History of Changes
Other Study ID Numbers: NETU-10-29
Study First Received: June 16, 2011
Results First Received: November 6, 2014
Last Updated: November 6, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Poland: Ministry of Health
Poland: Ethics Committee
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Ukraine: Ethics Committee
Ukraine: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Russia: Ethics Committee
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
India: Central Drugs Standard Control Organization
India: Institutional Review Board

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms
Signs and Symptoms, Digestive
Aprepitant
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Fosaprepitant
Palonosetron
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on November 25, 2014