| Participants |
Inclusion criteria
signed written informed consent male or female 18 years of age or older naïve to cytotoxic chemotherapy ‐ previous biological or hormonal therapy is permitted scheduled to receive first course of an anthracycline and cyclophosphamide‐containing MEC regimen for treatment of a solid malignant tumour: i.v. cyclophosphamide (500 to 1500 mg/m²) and i.v. doxorubicin (≥ 40 mg/m²) or i.v. cyclophosphamide (500 to 1500 mg/m²) and i.v. epirubicin (≥ 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 0, 1, or 2 female of non‐child‐bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is postmenopausal), or of child‐bearing potential with negative urine dipstick pregnancy test within 24 h before first dose of investigational product of Day 1 and with commitment to consistent and correct use throughout the clinical trial of one of the recommended contraceptive methods -
haematological and metabolic status adequate for receiving a moderately emetogenic regimen and meeting the following criteria:
total neutrophils ≥ 1500/mm³ (standard units: ≥ 1.5 × 10⁹/L) platelets ≥ 100,000/mm³ (standard units: ≥ 100.0 × 10⁹/L) bilirubin ≤ 1.5 × ULN -
liver enzymes
without known liver metastases, AST and/or ALT ≤ 2.5 × ULN with known liver metastases, AST and/or ALT ≤ 5.0 × ULN serum creatinine ≤ 1.5 mg/dL (standard units: ≤ 132.6 micromol/L) or creatinine clearance ≥ 60 mL/min
able to read, understand, and follow study procedures and complete patient diary
Exclusion criteria
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 scheduled to receive radiation therapy to abdomen or the pelvis within 1 week before Day 1 or between Days 1 and 5 in Cycle 1 any vomiting, retching, or mild nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 h before Day 1 symptomatic primary or metastatic CNS malignancy active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcaemia, active infection, or any uncontrolled medical condition (other than malignancy) that, in the opinion of the investigator, may confound results of the study, represent another potential aetiology for emesis and nausea (other than chemotherapy‐induced nausea and vomiting, CINV), or pose unwarranted risk in administering study drugs to the patient known hypersensitivity or contraindication to 5‐HT₃ receptor antagonists (e.g. palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron) or dexamethasone previously received an NK₁ receptor antagonist (e.g. aprepitant, casopitant) participated in a clinical trial involving oral netupitant administered in combination with palonosetron any investigational drug taken within 4 weeks before Day 1 Cycle 1 and/or scheduled to receive any investigational drug during the study systemic corticosteroid therapy at any dose within 72 h before Day 1 Cycle 1. However topical and inhaled corticosteroids with steroid dose ≤ 10 mg prednisone daily or its equivalent are permitted scheduled to receive bone marrow transplantation and/or stem cell rescue therapy any medication with known or potential antiemetic activity within 24 hours before Day 1 Cycle 1 scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1 week before 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 before Day 1 history or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block history of risk factors for torsades de pointes (heart failure, hypokalaemia, family history of long QT syndrome) severe cardiovascular disease, including myocardial infarction within 3 months before Day 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic congestive heart failure (CHF) NYHA Class III to IV, severe uncontrolled arterial hypertension any illness or condition that, in the opinion of the investigator, may confound results of the study or pose unwarranted risk 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
Mean/median age, years: n.r.
Gender: male + female
Tumour/cancer type: solid tumours
Chemotherapy regimen: MEC
Countries: Argentina, Brazil, Bulgaria, Croatia, Germany, Hungary, India, Italy, Mexico, Poland, Romania, Russian Federation, Ukraine, United States |
| Outcomes |
Primary endpoint
Secondary endpoints
CR during acute phase (0 to 24 h) CR during overall phase (0 to 120 h) proportion of patients with no emesis during delayed, acute, and overall phases proportion of patients with no rescue medication during delayed, acute, and overall phases proportion of patients with no significant nausea (visual analogue scale (VAS) < 25 mm) during delayed, acute, and overall phases proportion of patients with no nausea (VAS < 5 mm) during delayed, acute, and overall phases proportion of patients with complete protection (no emesis, no rescue medication, and no significant nausea (maximum nausea VAS < 25 mm)) during delayed, acute, and overall phases proportion of patients with total control (no emesis, no rescue medication, and no nausea (maximum VAS < 5 mm)) during delayed, acute, and overall phases severity of nausea, defined as maximum nausea on the VAS in acute, delayed, and overall phases time to first emetic episode, time to first rescue medication intake, and time to treatment failure (based on time to first emetic episode or time to first rescue medication intake, whichever occurs first) impact on daily life activities for the first 120 h following administration of MEC as assessed by the Functional Living Index‐Emesis (FLIE) questionnaire
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