resectable non-small cell lung cancer MedDRA version: 14.1 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
Product Name: AZD8931
Pharmaceutical Form: Film-coated tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
University Hospital of South Manchester NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 18 years or older. • Histologically confirmed NSCLC • Operable disease as determined by local staging investigations, including CT scan of thorax and abdomen, FDG-PET scan and mediastinoscopy where indicated as a standard of care. • Availability of surplus diagnostic biopsy tissue • WHO performance status 0 or 1 • Haematology (These measurements must be performed within two weeks prior to the patient going on study): Haemoglobin (Hb) > 9 g/dl Neutrophils > 1.5 x 10 9/L Platelets > 100 x 109/L Partial thromboplastin time (PTT) and Prothrombin time (PT) 50 ml/min as per calculated Cockcroft formula • Ability to give written informed consent according to ICH/GCP, and national/local regulations. • Ability to co-operate with study treatment and follow up Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Pregnancy. Only women of NONE child bearing potential may enter the study. Women must be permanently or surgically sterilized or postmenopausal* (see protocol for definitions). • Previous systemic treatment, radiotherapy or surgery for current lung cancer • Serious pre-existing medical co-morbidities, e.g. uncontrolled diabetes mellitus, uncontrolled respiratory or cardiac disease or ongoing or active infection (including HIV) • Psychiatric illness and/or social situation that would preclude study compliance • Prior (within the past 2 years) or concurrent malignancy (except adequately treated non-melanomatous skin cancer and resected cervical carcinoma in situ) • Baseline resting ECG with measurable QTc interval >480msec. • Echocardiogram confirming inadequate left ventricular function, LV ejection fraction180 mmHg or diastolic >100 mmHg), significant valvular disease or history of high risk dysrrhythmia (such as ventricular fibrillation or ventricular tachycardia [includes ventricular triplets]) • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease • Significantly impaired visual acuity • Medication that induces or inhibits CYP3A4 or reduces gastric acid production unless medically indicated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine whether a 40mg twice daily dose of AZD8931 administered for 10-14 days (up to 18 days if surgery recheduled) results in suppression of cancer cell growth, by looking at changes in a marker called Ki67, which represents proliferation of tumour cells, before and after treatment with AZD8931. ; Secondary Objective: Secondary endpoints • Tolerability and safety of AZD8931 up to 40 days post-operatively • Complete resection rate • Changes in expression of pharmacodynamic biomarkers of EGFR pathway activation as determined by Immunohistochemistry. Analysis to include, but not limited to p-EGFR, p-HER3, p-HER2, p-MAPK, p-Akt, p-STAT3 in tumour tissue obtained pre & post AZD8931 and in normal lung tissue. [targets will be evaluated subject to quantity of baseline (pre AZD8931 exposure) tissue available] • Tumour mutation status to include (but not limited to) the EGFR and K-RAS genes assessed using tissue obtained during surgery and circulating free DNA • Changes in levels of circulating cell death biomarkers (M30,65) • Changes in levels of circulating HER family ligands before, during and after AZD8931 exposure. • Plasma levels of AZD8931 at day 3, 8, the day before and immediately prior to surgery. ;Primary end point(s): Reduction in Ki-67 proliferation index (percentage of tumour cells stained positive for Ki-67 in the sample) measured by immunohistochemistry in surgically resected samples compared to biopsy tissue obtained prior to AZD8931 dosing. | — |
Countries
United Kingdom
Outcome results
None listed