Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Lenograstim

Antimitotic Agents

Adavosertib

Enzyme Inhibitors

AZD 1775, antimitotic agent + pegfilgrastim 21 day Cycle, maximum of 4 cycles

Placebo + antimitotic+pegfilgrastim 21 day cycle, maximum of 4 cycles

AZD 1775 + antimitotic agent+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity

AZD1775

Placebo (to match dose) + antimitotic+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity

AZD1775 Placebo

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.

Antimitotic Agent

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.

pegfiligrastim

David R Spigel, MD

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.

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

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.

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.

AstraZeneca

Adverse event data were collected from the time the first patient received the first dose of investigational drug on May 20, 2014 until the study was closed on May 12, 2015.

Six subject safety lead-in followed by single arm cohort. All patients were to receive AZD 1775 plus Docetaxel in 21 day cycles for a maximum of 4 cycles.

Part A: AZD1775 Plus Docetaxel

Age, Continuous

< 65

>= 65

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Smoker

Non-Smoker

Smoking Status Missing

Tobacco Use

ECOG Performance Status = 0

ECOG Performance Status = 1

ECOG scores are defined as follows:

0 - Asymptomatic (Fully active, able to carry on all predisease activities without restriction)

1. - Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.)
2. - Symptomatic, \< 50% of time in bed during the day.
3. - Symptomatic, \>50% in bed, but not bedbound.
4. - Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)
5. - Death

ECOG Performance Status

The sponsor terminated the study early. The study was closed on May 12, 2015. Part B of the study was not done.

Charles H. Davis

The study was terminated early by the sponsor. Pharmacokinetic data have not been analyzed.

Pharmacokinetic Profile of AZD 1775 in Combination With Docetaxel

Thirty-two (32) subjects were enrolled in Part A, but the study was terminated early. Patients on-study at the time the study was terminated have been censored.

Spots Global Cancer Trial Database for pegfiligrastim