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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
AZD 1775 + antimitotic agent+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity
Placebo (to match dose) + antimitotic+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity
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.
Research Site
Birmingham, Alabama, United States
Research Site
Scottsdale, Arizona, United States
Research Site
Fayetteville, Arkansas, United States
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.
Time frame: Up to 20 months
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.
Time frame: Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity
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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.
Research Site
Englewood, Colorado, United States
Research Site
Orlando, Florida, United States
Research Site
Wichita, Kansas, United States
Research Site
Louisville, Kentucky, United States
Research Site
Durham, North Carolina, United States
Research Site
Cincinnati, Ohio, United States
Research Site
Pittsburgh, Pennsylvania, United States
...and 2 more locations