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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Previously Treated Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AZD1775
* Drug: AZD1775 Placebo
* Drug: Antimitotic Agent
* Drug: pegfiligrastim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD 1775, antimitotic, pegfilgrastim<br>AZD 1775, antimitotic agent + pegfilgrastim 21 day Cycle, maximum of 4 cycles | Drug: AZD1775<br>* AZD 1775 + antimitotic agent+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity<br>* Other names: MK-1775; Neulasta;Drug: Antimitotic Agent<br>* The antimitotic is a drug that stops cells from dividing. This leads to cell death. Because cancer cells divide faster than normal cells, they are more likely than normal cells to be affected by this drug.<br>* Other names: antiimitotic agent;Drug: pegfiligrastim<br>* Pegfilgrastim is a man-made version of a protein called granulocyte-colony stimulating factor (G-CSF). This protein is made by cells in the body to stimulate the bone marrow to make more infection-fighting white blood cells.Pegfilgrastim is made by attaching filgrastim to a molecule called polyethylene glycol (PEG). This addition helps it stay in the body longer than filgrastim, which means it can be given less often.<br>* Other names: Neulasta;|
| Placebo Comparator: Placebo + antimitotic + pegfilgrastim<br>Placebo + antimitotic+pegfilgrastim 21 day cycle, maximum of 4 cycles | Drug: AZD1775 Placebo<br>* Placebo (to match dose) + antimitotic+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity<br>* Other names: MK-1775; Neulasta;Drug: Antimitotic Agent<br>* The antimitotic is a drug that stops cells from dividing. This leads to cell death. Because cancer cells divide faster than normal cells, they are more likely than normal cells to be affected by this drug.<br>* Other names: antiimitotic agent;Drug: pegfiligrastim<br>* Pegfilgrastim is a man-made version of a protein called granulocyte-colony stimulating factor (G-CSF). This protein is made by cells in the body to stimulate the bone marrow to make more infection-fighting white blood cells.Pegfilgrastim is made by attaching filgrastim to a molecule called polyethylene glycol (PEG). This addition helps it stay in the body longer than filgrastim, which means it can be given less often.<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Response evaluation is determined by using Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions assessed by medical imaging scan (e.g. CT or MRI). The same method of assessment and the same technique was to be used to characterize each identified and reported lesion at baseline and during subsequent imaging procedures. The objective response rate is defined as the percentage of patients with a confirmed best overall response of Complete Response (CR) or Partial Response (PR). Complete Response is defined as disappearance of all target lesions since baseline. Any pathological lymph nodes selected as target lesions must have a reduction in short axis to < 10 mm. Partial Response is defined as at least a 30% decrease in the sum of the diameters of the Target Lesion, taking as reference the baseline sum of diameters. | Up to 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Profile of AZD 1775 in Combination With Docetaxel | Venous blood samples taken for determination of AZD1775, metabolites of 1775 on Cycle 1, Day 1 pre-dose and 2 hours post dose, Cycle 2 Day 1 pre-dose and 2 hours post dose, and Cycle 4 pre-dose and 2 hours post dose. However, the study was terminated early by the sponsor; therefore, pharmacokinetic data were not collected. | Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC