A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer

Exclusion Criteria

• •Cycle 1:
• •1. Lactating patient.
• •2. Current use of illicit drugs or current evidence of alcohol abuse.
• •3. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 and up to Day 1 of Cycle 2.
• •4. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5, inclusive.
• •5. Any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day 1.
• •6. Symptomatic primary or metastatic central nervous system (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 hydroxytryptamine type 3 (5-HT3) receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron), to dexamethasone, or to neurokinin-1 (NK1) receptor antagonists (e.g., aprepitant, rolapitant).
• •9. Known contraindication to the IV administration of 50 mL 5% glucose solution.
• •10. Participation in a previous clinical trial involving IV fosnetupitant or oral netupitant administered alone or in combination with palonosetron.
• •11. Any investigational drugs taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug (other than those planned by the study protocol) during the present study.
• •12. Systemic corticosteroid therapy within 72 hours prior to the start of AC chemotherapy administration on Day 1, except the dexamethasone provided as additional study drug. However, topical and inhaled corticosteroids are permitted.
• •13. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy during the study participation.
• •14. Other than as administered as part of the study protocol, any medication with known or potential antiemetic activity within 24 hours prior to the start of AC chemotherapy administration on Day 1, including:
• •* 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron)
• •* NK1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant 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 cannabinoids (e.g., tetrahydrocannabinol or nabilone)
• •* Over The Counter (OTC) antiemetics, OTC cold or OTC allergy medications.
• •15. Scheduled to receive any strong or moderate inhibitor of CYP3A4 during the efficacy assessment period (Day 1 to Day 5, inclusive) or its intake within 1 week prior to Day 1.
• •16. Scheduled to receive any CYP3A4 inducer during the efficacy assessment period (Day 1 to Day 5, inclusive) or its intake within 4 weeks prior to Day 1, with the exception of corticosteroids (for which exclusion criterion #12 applies).
• •17. History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
• •18. History of risk factors for Torsades de Pointes (heart failure, hypokalemia, family history of Long QT Syndrome).
• •19. Severe or uncontrolled 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) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension.
• •Cycles 2 to 4:
• •1. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 of current cycle and up to Day 1 of the next cycle.
• •2. Active infection or uncontrolled disease that may pose unwarranted risks in administering the study drugs to the patient.
• •3. Started any of the prohibited medications.
• •4. Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day 1.
• •5. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5.
• •6. Symptomatic primary or metastatic CNS malignancy.
• •7. Any illness or medical condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product or dexamethasone to the patient.