A Placebo Controlled Study Comparing AZD1775+ Docetaxel Versus Placebo+Docetaxel to Treat Lung Cancer

A Lead-in Phase II Multicentre, Randomised, Double-Blind Study Comparing AZD1775 Plus Docetaxel and Placebo Plus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer Patients

A Lead-in Phase II Multicentre, Randomised, Double-Blind Study Comparing AZD1775 plus antimitotic agent and Placebo plus an antimitotic agent in Previously Treated Non-Small-Cell Lung Cancer Patients

This multicentre trial consists of an open-labelled single cohort lead-in (Part A) followed by a phase II double-blind, randomised, placebo-controlled comparison of AZD1775 (or placebo) and an antimitotic agent. Review by a central laboratory of fresh tumour or archival tumour samples will be required prior to study entry to assess TP53 mutation status. However, subjects will be allowed to enter the single cohort (Part A) regardless of TP53 mutation status (wild-type or mutant). In addition, patients in the single cohort Part A treatment group will be asked to consent to limited sample collections for assessment of pharmacokinetic parameters.

Inclusion Criteria

• Provision of informed consent prior to any study specific procedures
• Histologic or cytologic diagnosis of advanced NSCLC, excluding large cell neuroendocrine, and mixed NSCLC/small-cell histologies
• Failure of one prior platinum-based doublet treatment for advanced NSCLC (either due to progressive disease or toxicity)
• Measurable disease as measured by Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Mandatory availability of tumour tissue (archival or fresh if archival is not available) for TP53 testing
• Male or female ≥18 years-of-age
• Subjects may have received radiation for palliation prior to starting study treatment if they have recovered from the side effects of such therapy
• Absolute neutrophil count (ANC) ≥1500/μL
• Haemoglobin (Hgb) ≥9 g/dL
• Platelets ≥100,000/uL
• Adequate liver function defined as:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal limits (WNL) or ≤2.5 x upper limit of normal (ULN), if liver metastases are present
• Serum bilirubin WNL
• Adequate renal function
• Ability to swallow oral medication
• Fertile male subjects willing to use at least one medically acceptable form of birth control for the duration of the study and for 2 weeks after treatment stops
• Female subjects who are not of childbearing potential and fertile female subjects of childbearing potential who agree to use adequate contraceptive measures
• Predicted life expectancy ≥12 weeks
• Willingness and ability to comply with study and follow-up procedures
• Ability to understand the investigational nature of this study and give written informed consent
• Most recent chemotherapy ≤21 days or have not recovered from the side effects > Grade 1.
• Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting AZD1775 or has not recovered from side effects of such therapy
• Major surgical procedures ≤28 days of beginning AZD1775, or minor surgical procedures ≤7 days
• Known central nervous system (CNS) disease
• Any known hypersensitivity or contraindication to the components of study treatment (AZD1775 and docetaxel)
• Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association [NYHA] ≥ Class 2
• Pregnant or lactating
• Concurrent administration of medications or foods that are strong inhibitors of
• Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the subject to receive protocol treatment
• Presence of other active cancers, or history of treatment for invasive cancer ≤3 years
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol