Optimalt tidspunkt for at skifte behandling fra Tarceva til Tagrisso.
- Conditions
- ung CancerMedDRA version: 20.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-005637-47-DK
- Lead Sponsor
- Department of Oncology, Aarhus University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
1.Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
2.Age > 18 years
3.Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy
4.Detection of T790M in blood test verified by a quantitative stable or increase in T790M level in an additional blood test taken sequential within 7 days
5.Prior therapy with erlotinib until point of randomization as defined by positive T790M status
6.World Health Organization (WHO) performance status 0-3
7.Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline
8.ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6
9.Female patients of childbearing potential must be using adequate contraceptive measures.
10.Male patients must be willing to use barrier contraception, i.e., condoms.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1.Previous (within 6 months) or current treatment with AZD9291
2.Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 (Appendix C)
3.Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator’s opinion would significantly alter the risk/benefit balance.
4.Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration
5.Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
6.Any of the following cardiac criteria:
a.Mean resting corrected QT interval (QTcF) > 470 ms.
b.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)
c.Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
7.Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment
8.History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To study the optimal time for shifting treatment with erlotinib to osimertinib, when tha patient has developed resistance mutation (T790M).;Secondary Objective: Study the resistance mechanisms developing during osimertinib treatment;Primary end point(s): To describe temporal changes in the levels of T790M and to explore the effect of these changes on disease progression according to RECIST 1.1. An elevated level of T790M is considered valid if it increases to 1.5 times the baseline value, which should be confirmed in a second blood sample taken approximately one week apart. The time from randomisation to elevated T790M may also be evaluated if feasible.;Timepoint(s) of evaluation of this end point: Time from randomization to development of disease progression.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival (PFS1) measured from date of randomisation until the date of objective radiological disease progression (assessed via RECIST 1.1) or death (by any cause in the absence of disease progression).<br>Time to second progression (PFS2) measured from date of randomisation to date of the progression event (assessed via RECIST 1.1) subsequent to that used for PFS1 or death. This endpoint is relevant only to the patients randomised to the erlotinib continuation arm who switch to AZD9291 treatment.;Timepoint(s) of evaluation of this end point: Time from randomization to development of progression (RECIST 1.1). See abiove.