Clinical trial to assess the feasibility and the activity of osimertinib on patients with non small cell lung cancer
- Conditions
- SCLC patientsTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001834-82-ES
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 156
Registration
• Pathological diagnosis of adenocarcinoma of the lung carrying common EGFR activating mutations associated with EGFR-TKI sensitivity (Del19 or L858R); performed locally; no other EGFR mutations will be allowed. In case of other (than EGFR) concomitant mutations, discussion with EORTC Headquartes is mandatory;
• Stage IV NSCLC;
• Blood sample available for cfDNA EGFR T790M central testing;
• Adequate tissue sample in quantity and quality for translational research;
• Age =18 years;
• EGFR TKI treatment-naïve eligible to receive first-line treatment with EGFR TKI;
• Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if performed more than 12 months before registration;
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
Randomization
• Report of adequacy sample for cfDNA EGFR T790M test by central laboratory;
• Prior palliative radiotherapy or surgical procedures are allowed if completed at least 4 weeks before randomization;
• Patients with brain metastases are allowed provided they are 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;
•Baseline tumor assessment scans are done within 21 days before randomization
• Evaluable disease as defined below;
• At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes which must have a short axis of =15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and which is suitable for accurate repeated measurements.
• WHO Performance Status 0-2, with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks;
• Adequate bone marrow, renal, hepatic and liver function within 21 days form randomization and defined in the protocol;
• No significant comorbidity that according to the investigator would hamper the participation on the trial;
• Female patients should be using adequate contraceptive measures, as defined by the investigator, during the treatment until 2 months after last dose of osimertinib. They should not be breastfeeding, and must have a negative pregnancy test (serum or urine) prior to first dose of study drug (within 72 hours); or female patients must have an evidence of non-child-bearing potential by fulfilling one of the criteria defined in the protocol at screening;
• Male patients should be willing to use barrier contraception, i.e., condoms as defined by the investigator, during the treatment until 4 months after last dose of osimertinib;
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46
• Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug;
• Prior treatment with an EGFR-TKI;
• Major surgery (excluding placement of vascular access) within 4 weeks before randomization;
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks before randomization.
• Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of study drug) medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 ; antiacids could be taken in a time-separate manner, at least 8 hours from gefitinb;
• Other anti-cancer therapies and alternative medications such as homeopathie, etc;
• Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known;
• Leptomeningeal carcinomatosis; spinal cord compression;
• Any unresolved toxicities from prior systemic therapy (e.g., adjuvant chemotherapy) greater than CTCAE grade 2 at the time of randomization;
• Patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or localized cervical cancer or localised and presumed cured prostatic cancer) within 2 years before randomization and are not receiving specific treatment for these malignancies at baseline assessment;
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol;
• Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Active infection will include any patients receiving intravenous treatment for infection; active hepatitis B infection will, at a minimum, include all patients who are Hepatitis B surface antigen positive (HbsAg positive) based on serology assessment. Screening for chronic conditions is not required;
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant gastrointestinal resection that would preclude adequate absorption of osimertinib or gefitinib;
• 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)
• Past medical history of ILD (Interstitial Lung Disease), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method