EUCTR2015‐001800‐74.

Methods	Randomised, phase 3, active‐controlled study Recruitment period: December 2015 to n.r. target sample size: 400  Masking: double‐blind Baseline patient characteristics: n.r.
Participants	Inclusion criteria signed written informed consent male or female 18 years of age or older histologically or cytologically confirmed solid tumour malignancy naïve to cytotoxic chemotherapy 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 i.v. dose of 70 mg/m² cyclophosphamide 1500 mg/m² carmustine (BCNU) > 250 mg/m² dacarbazine (DTIC) mechlorethamine (nitrogen mustard) if a patient is female, she shall be: of non‐child‐bearing potential; or of child‐bearing potential and using reliable contraceptive measures and having a negative urine pregnancy test haematological and metabolic status adequate for receiving HEC regimen and meeting the following criteria: total neutrophils 1500/mm³ platelets 100,000/mm³ bilirubin 1.5 × ULN adequate liver enzymes adequate serum creatinine able to read, understand, and follow study procedures and complete patient diary Exclusion criteria lactating woman active infection or uncontrolled disease except for malignancy that may pose unwarranted risk in administering 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 scheduled to receive radiation therapy to abdomen or pelvis within 1 week before start of reference chemotherapy administration on Day 1 or between Days 1 and 5 any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute) within 24 h before start of 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 NK₁ receptor antagonists known contraindication to i.v. administration of 50 mL 5% glucose solution previously received an NK₁ receptor antagonist participated in a previous clinical trial involving i.v. 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 before Day 1 and/or scheduled to receive any investigational drug during the present study systemic corticosteroid therapy at any dose within 72 h before start of reference chemotherapy administration on Day 1 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 before Day 1 scheduled to receive any of the following CYP3A4 substrates within 1 week before Day 1: terfenadine, cisapride, astemizole, pimozide received within 4 weeks before Day 1 or scheduled to receive any CYP3A4 inducer any medication with known or potential antiemetic activity within 24 h before start of reference chemotherapy administration on Day 1 Cycle 1, including: 5‐HT₃ receptor antagonists NK₁ receptor antagonists benzamide phenothiazines benzodiazepines (except if the patient is receiving such medication for sleep or anxiety and has been on a stable dose for at least 7 days before Day 1) butyrophenones anticholinergics antihistamines domperidone mirtazapine olanzapine prescribed cannabinoids over‐the‐counter (OTC) antiemetics, OTC cold and allergy medications history of or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block history of torsades de pointes or known history of risk factors for torsades de pointes severe cardiovascular disease diagnosed within 3 months before Day 1 Cycle 1, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic congestive heart failure (CHF) NYHA Class III to IV, and 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 investigational product to the patient concurrent medical condition that would preclude administration Mean/median age, years: n.r. Gender: male + female Tumour/cancer type: solid tumour malignancy Chemotherapy regimen cisplatin administered as a single i.v. dose of 70 mg/m² cyclophosphamide 1500 mg/m² carmustine (BCNU) > 250 mg/m² dacarbazine (DTIC) mechlorethamine (nitrogen mustard) Country: Austria, Croatia, Czech Republic, Germany, Israel, Italy, Poland, Serbia, South Africa, Spain, Ukraine, United States
Interventions	pro‐netupitant (260 mg) + palonosetron (0.25 mg) + dexamethasone
Outcomes	Primary endpoints physical examination  vital signs 12‐lead electrocardiogram  laboratory test (haematology, blood chemistry, urinalysis) adverse events (AEs) assessment Secondary endpoints proportion of patients with complete response (no emetic episodes and no rescue medication) during acute, delayed, and overall phases proportion of patients with no emetic episodes during acute, delayed, and overall phases proportion of patients with no significant nausea (visual analogue scale (VAS) < 25 mm) during acute, delayed, and overall phases (because VAS is assessed daily, for delayed and overall phases, the maximum VAS value in the relevant phase will be considered)
Notes	main ID: EUCTR2015‐001800‐74‐DE primary sponsor: Helsinn Healthcare SA