a safety study of intravenous pro-netupitant and palonosetron combination for the prevention of nausea and vomiting

Conditions: Chemotherapy-Induced Nausea and Vomiting

Summary: nepa-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two antiemetic drugs, given with oral dexamethasone. the objective of the study is to evaluate if pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.


Eligibility criteria:
inclusion criteria: cycle 1 * signed written informed consent * histologically or cytologically confirmed solid tumor malignancy. * naïve to cytotoxic chemotherapy. previous biological or hormonal therapy will be permitted. * scheduled to receive at least 4 repeated consecutive cycles of the following highly emetogenic reference chemotherapies (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) * eastern cooperative oncology group (ecog) performance status of 0, 1, or 2 . * if a patient is female, she shall be of non-childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. * hematologic and metabolic status adequate for receiving an highly emetogenic regimen based on laboratory criteria (total neutrophils,platelets, bilirubin, liver enzymes, serum creatinine or creatinine clearance) * able to read, understand, follow the study procedure and complete patient diary. cycles 2 to 4: the following inclusion criteria must be checked prior to inclusion at each repeated cycle: * participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator and does not pose unwarranted risk to the patient. * scheduled to receive the same chemotherapy regimen as cycle 1 or one of the reference chemotherapies as defined in inclusion criterion 5 for cycle 1. * if a patient is female, she shall be of non--childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. * adequate hematologic and metabolic status according to the investigator's opinion. exclusion criteria: cycle 1 * lactating woman. * active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient. * current use of illicit drugs or current evidence of alcohol abuse. * scheduled to receive moderately or highly emetogenic chemotherapies from day 2 to day 5. * received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on day 1 or between days 1 to 5. * any vomiting, retching, or nausea (grade ≥ 1 as defined by national cancer institute) within 24 hours prior to the start of the reference chemotherapy administration on day 1. * symptomatic primary or metastatic cns malignancy. * known hypersensitivity or contraindication to 5-ht3 receptor antagonists, to dexamethasone or to nk-1 receptor antagonists. * known contraindication to the iv administration of 50 ml 5% glucose solution. * previously received an nk-1 receptor antagonist. * participation in a previous clinical trial involving iv pro-netupitant or oral netupitant administered alone or in combination with 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 present study. * systemic corticosteroid therapy at any dose within 72 hours prior to the start of reference chemotherapy administration on day 1. topical and inhaled corticosteroids are permitted. * 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 within 1 week prior to day 1: terfenadine, cisapride, astemizole, pimozide. * received within 4 weeks prior to day 1 or scheduled to receive any cyp3a4 inducer. * any medication with known or potential antiemetic activity within 24 hours prior to the start of reference chemotherapy administration on day 1 of cycle 1, including but not limited to 5-ht3 receptor antagonists and nk-1 receptor antagonists * history or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block * history of torsade de point or known history of risk factors for torsade de point (heart failure, hypokalemia, family history of long qt syndrome). * severe cardiovascular diseases diagnosed within 3 months prior to day 1 of first cycle, including myocardial infarction, 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. * 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. cycles 2 to 4: the following exclusion criteria must be checked prior to inclusion in each repeated cycle: * lactating woman. * active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient. * started any of the restricted medications. * any vomiting, retching, or nausea (grade ≥ 1 as defined by national cancer institute) within 24 hours prior to the start of reference chemotherapy administration on day 1. * received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on day 1 or between days 1 to 5. * symptomatic primary or metastatic cns malignancy.