To investigate safety and efficacy of AZD9291 when given orally to patients with EGFRm+/T790M+ non small cell lung cancer. Patients will be chosen from those who have already been prescribed an EGRf TKI medicine (such as Iressa or Tarceva)

Phase 1

Conditions: on Small Cell Lung Cancer
MedDRA version: 16.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-000531-17-IT

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 175

Inclusion Criteria

Locally advanced/metastatic NSCLC.
Radiological documentation of disease progression following 1st line EGFR TKI treatment or following minimum prior therapy with an EGFR TKI and platinum-containing doublet chemotherapy.
Confirmation the tumour harbours EGFR and T790 mutation.
WHO status 0-1; min life expectancy of 12 weeks.
At least one measurable lesion at baseline by CT/MRI.
Females of child-bearing potential using contraception; negative pregnancy test.

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 79
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 96

Exclusion Criteria

Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 (or 3rd generation TKIs); major surgery within 4 weeks; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; current treatment with potent inhibitors of CYP2C8 and potent inhibitors/inducers of CYP3A4.
Unresolved toxicities from prior therapy.
Unstable spinal cord compression/brain metastases.
Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection.
Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection.
Cardiac disease.
Past history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
Inadequate bone marrow reserve or organ function.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of AZD9291 by assessment of Objective Response Rate (ORR);Secondary Objective: To further assess the efficacy of AZD9291 in terms of: <br> - Progression Free Survival (PFS)<br> - Duration of Response (DoR)<br>- Disease Control Rate (DCR)<br>- Tumour shrinkage<br> - Overall Survival (OS)<br>To assess the safety and tolerability profile of AZD9291.<br>To investigate the effect of AZD9291 on QTc interval after oral dosing to NSCLC patients.<br>To assess the impact of AZD9291 on patients’ disease-related symptoms and health related quality of life (HRQoL).<br>To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550).<br>;Primary end point(s): ORR according to RECIST 1.1 by an Independent Central Review (ICR).<br>Sensitivity analysis of ORR using investigators assessments of RECIST.<br>;Timepoint(s) of evaluation of this end point: Every 6 weeks relative to first dose until disease progression

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): PFS, DoR, DCR according to RECIST 1.1 using assessments performed by an ICR.<br>Sensitivity analysis of PFS, DoR, DCR, tumour shrinkage using investigators assessments of RECIST.<br>Description of OS.<br>Adverse events (graded by CTCAE v4)<br>- Clinical chemistry, haematology and urinalysis<br>- Vital signs, Physical Examination, Weight<br>- Digital ECG<br>- WHO Performance Status<br>QT interval by digital ECG<br>EORTC QLQ-C30<br>EORTC QLQ LC13<br>PK exposure parameters: (Cmax) (Css max), (tmax),(tss max), (AUC(0-24)),(AUCss), (Css min), (CLss/F) (RAC) <br>The ratio of metabolite to AZD9291 will also be calculated.<br><br><br>;Timepoint(s) of evaluation of this end point: Efficacy every 6 weeks, Safety and Health related quality of life throughout study, PK exposure Cycles 1 to 3.

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