E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
resectable non-small cell lung cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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) < 1.5 x ULN • Hepatic function Serum bilirubin < 1.5 x upper limit of normal (ULN) Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) < 2.5 X ULN • Adequate renal function (calculated clearance > 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
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E.4 | Principal 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 fraction<45%. • Known uncontrolled or symptomatic angina, arrhythmias or congestive heart failure, evidence of transmural infarction on ECG, poorly controlled hypertension (systolic >180 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
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial endpoint will be the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |