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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02087176
Other study ID # D6011C00001
Secondary ID
Status Completed
Phase Phase 2
First received March 7, 2014
Last updated June 10, 2015
Start date March 2014
Est. completion date May 2015

Study information

Verified date June 2015
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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


Description:

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


Recruitment information / eligibility

Status Completed
Enrollment 48
Est. completion date May 2015
Est. primary completion date May 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
AZD1775
AZD 1775 + antimitotic agent+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity
AZD1775 Placebo
Placebo (to match dose) + antimitotic+ pegfilgrastim, restage every 2 cycles; continue until disease progression or unacceptable toxicity
Antimitotic Agent
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.
pegfiligrastim
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.

Locations

Country Name City State
United States Research Site Birmingham Alabama
United States Research Site Cincinnati Ohio
United States Research Site Durham North Carolina
United States Research Site Englewood Colorado
United States Research Site Fayetteville Arkansas
United States Research Site Louisville Kentucky
United States Research Site Milwaukee Wisconsin
United States Research Site Nashville Tennessee
United States Research Site Orlando Florida
United States Research Site Pittsburgh Pennsylvania
United States Research Site Scottsdale Arizona
United States Research Site Wichita Kansas

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective Response Rate The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline. Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity No
Primary Disease Control Rate The disease control rate is defined as the percentage of full analysis set subjects with a best overall response of CR, PR or SD). Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity No
Primary Progression Free Survival (PFS) PFS is defined as the time from randomisation, or date of study drug administration in the open label phase, until the date of objective disease progression or death by any cause in the absence of progression Up to projected 20 months, subjects will be restaged after every 2 cycles in Part B (every 6 weeks) continue until disease progression or unacceptable toxicity No
Secondary Safety and Tolerability of AZD1775 and an antimiotic in previsously treated NSCLC patiients Assessed in terms of adverse events and laboratory data that is collected on all patients Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity Yes
Secondary Pharmacokinetic profile of AZD 1775 in combination with an antimitotic Venous blood samples taken for determination of AZD1775, metabolites of 1775 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 Up to projected 20 months, subjects will be restaged after every 2 cycles (every 6 weeks.) continue until disease progression or unacceptable toxicity Yes
Secondary Compare Objective Response Rate and Disease Control Rate between arms The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline. The disease control rate is defined as the percentage of FAS subjects with a best overall response of CR, PR or SD. Up to projected 20 months, Subjects will be restaged after every 2 cycles in Part B (every 6 weeks) continue until disease progression or unacceptable toxicity No
Secondary Assess the duration of response (DoR) and overall survival in each treatment arm Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death. Overall survival is defined as the time from the date of randomization until death due to any cause. Up to projected 20 months, assessed every 6 weeks continue until disease progression or any cause death No
Secondary Safety of AZD 1775 in combination with an antimiototic Assessed in terms of adverse events and laboratory data that is collected on all patients Up to projected 20 months , at every Visit Yes