Advanced or metastatic untreated EGFR mutation positive NSCLC MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Vizimpro 45 mg compresse rivestite con film
Product Name: dacomitinib
Product Code: [NAP]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: dacomitinib
CAS Number: 1110813-31-4
Sponsors
FONDAZIONE RICERCA TRASLAZIONALE (FORT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Written informed consent; 2) Male or female patient aged =18 years; 3) Histologically/cytologically confirmed diagnosis of NSCLC with evidence of activating EGFR mutations including exon 19 deletion, exon 21 L858R or other activating/sensitizing EGFR mutations such as exon 21 L861Q, exon 18 G719S, G719A, G719C, exon 20 S768I and V769L; co-occurrence of de novo T790M is not an exclusion criterion; EGFR status assessed in circulating DNA is allowed; 4) Patients with brain metastases are allowed provided they are asymptomatic and stable (i.e. without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and without deterioration of any neurologic symptoms), and have not received steroids for at least 7 days before randomization; 5) No evidence of concomitant drivers including KRAS mutations, HER2 mutations, ALK or ROS1 rearrangements, MET mutations, BRAF mutations; 6) No previous EGFR-TKI therapy; Previous palliative radiotherapy or surgery allowed. Previous neo/adjuvant chemotherapy is allowed as long as therapy was completed at least 6 months before diagnosis of advanced or metastatic NSCLC; 7) At least one radiological measurable disease according to RECIST criteria version 1.1; 8) Performance status 0-1 (ECOG PS); 9) Patient compliance to trial procedures; 10) Adequate bone marrow function (ANC = 1.5x109/L, platelets =100x109/L, haemoglobin >9 g/dl); 11) Adequate liver function (AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN, bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 89
Exclusion criteria
Exclusion criteria: 1) Previous therapy with any EGFR-TKI; 2) Previous systemic anti-cancer therapy for advanced/metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug; 3) Absence of measurable lesions; 4) Concomitant radiotherapy or chemotherapy; 5) Symptomatic or immediately requiring therapy brain metastases or carcinomatous meningitis. Subjects with asymptomatic and stable or treated brain metastases may participate 6) Diagnosis of any other malignancy during the last 3 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin; 7) History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis); 8) Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV); 9) Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of the study drugs; 10) Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs using local clinic ECG machine-derived QTcF value; • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec or history of episodes of bradycardia (<50 BPM); • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval; • Abnormal cardiac function: LVEF < 50% (assessed by MUGA or ECHO) 11) Pregnancy or lactating female; 12) Other serious illness or medical condition potentially interfering with the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the best drug sequencing in patients with advanced or metastatic EGFR mutation positive NSCLC. The study, including patients with classical or uncommon activating EGFR mutations, will allow to investigate the efficacy of dacomitinib or osimertinib in these patients. Patients with asymptomatic or controlled brain metastases are eligible, allowing to define efficacy of dacomitinib in this special population.;Secondary Objective: •OS in patients treated with osimertinib first followed by dacomitinib and in patients treated with dacomitinib first followed by osimertinib •PFS at the time of study second-line therapy failure (PFS2) in patients treated with front-line osimertinib or dacomitinib; •PFS in patients treated with osimertinib first or dacomitinib first; •Response Rate (RR) with dacomitinib or osimertinib; •RR, PFS and OS with osimertinib followed by dacomitinib or with the opposite sequence in patients with uncommon activating EGFR mutations; •RR, PFS and OS with dacomitinib given at the time of osimertinib failure; •Intracranial RR and intracranial PFS with dacomitinib or osimertinib •Safety and incidence of AEs in patients treated with osimertinib followed by dacomitinib or with the opposite sequence.;Primary end point(s): OS in patients treated with osimertinib first or dacomitinib first;Timepoint(s) of evaluation of this end point: Continuous - Every 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • OS in patients treated with osimertinib first followed by dacomitinib and in patients treated with dacomitinib first followed by osimertinib • PFS at the time of study second-line therapy failure (PFS2) in patients treated with front-line osimertinib or dacomitinib; • PFS in patients treated with osimertinib first or dacomitinib first; • Response Rate (RR) with dacomitinib or osimertinib; • RR, PFS and OS with osimertinib followed by dacomitinib or with the opposite sequence in patients with uncommon activating EGFR mutations; • RR, PFS and OS with dacomitinib given at the time of osimertinib failure; • Intracranial RR and intracranial PFS with dacomitinib or osimertinib • Safety and incidence of AEs in patients treated with osimertinib followed by dacomitinib or with the opposite sequence.;Timepoint(s) of evaluation of this end point: • 24 years from LPFV • continuous - every 8 weeks • continuous - every 8 weeks • continuous - every 8 weeks and 24 years from LPFV • continuous - every 8 weeks and 24 years from LPFV • continuous - every 8 weeks • continuous | — |
Countries
Austria, France, Germany, Italy, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactClinical Operations
Clinical Research Technology
Outcome results
None listed