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Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.

AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of the WEE 1 kinase that sensitizes tumor cells to cytotoxic agents and is being developed for the treatment of advanced solid tumors and p53 pathway deficient malignancies

AZD1775

AZD1775 Matching Placebo

This drug is a part of a general group of chemotherapy drugs called anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, this drug helps to stop the growth of cancer cells.

pemetrexed

This drug is a platinum chemotherapy drug that acts like an alkylating agent. It stops the growth of cancer cells, causing the cells to die.

carboplatin

David R Spigel, MD

The aim of this study is to combine AZD1775 with standard front-line chemotherapy in subjects with advanced NSCLC.

This is a randomised, phase II trial comparing AZD1775 plus pemetrexed and carboplatin followed by maintenance AZD1775 and pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed in patients with previously untreated metastatic non-squamous NSCLC with TP53 mutations. The primary endpoint of the trial is assessment of progression-free survival (PFS).

Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer

A Phase II Study of AZD1775 Plus Pemetrexed and Carboplatin Followed by a Randomised Comparison of Pemetrexed and Carboplatin With or Without AZD1775 in Patients With Previously Untreated Stage IV Non-Squamous Non-Small-Cell Lung Cancer

Progression free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.

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).

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.

AstraZeneca

Adverse event data were collected from the time the first patient received the first dose of investigational drug on March 19, 2014 until the study was closed on June 1, 2015.

AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6

Cohort 1

AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6.

Cohort 2

AZD1775 175 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6

Cohort 3

AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5.

Cohort A

AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21- Day Cycle)/Pemetrexed 400 mg/Carboplatin AUC 5

Total

Age, Continuous

< 65

>= 65

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Smoker

Non-Smoker

Tobacco Use

ECOG Performance Status = 0

ECOG Performance Status = 1

The Eastern Cooperative Oncology Group (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 and able to carry out work of a light or sedentary nature); 2 = Symptomatic, \<50% in bed during the day; 3 = Symptomatic, \>50% in bed, but not bedbound; 4 = Bedbound (Completely disabled. Cannot carry on any self-care; 5 = Dead

ECOG Performance Status

The study was terminated on June 1, 2015 by the sponsor. The Primary Outcome Measure (Progression Free Survival) was not assessed and the randomised portion of the study was not done.

Charles H. Davis

AZD1775 225 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6.

Progression-Free Survival data were not collected.

Progression Free Survival

AZD1775 225 mg bid. 5 doses over 3 days (Days 3, 4, and 5 of a 21- Day Cycle)/Pemetrexed 500 mg/Carboplatin AUC 6

Assess the Objective Response Rates in Each Arm

AZD1775 125 mg bid. 5 doses over 3 days (Days 1, 2, and 3 of a 21-Day cycle)/Pemetrexed 400 mg/Carboplatin AUC 5

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer	NCT02087241	Previously Untr...	AZD1775 AZD1775 Matchin... pemetrexed carboplatin	18 Years -	AstraZeneca
Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer	NCT02087241	Previously Untr...	AZD1775 AZD1775 Matchin... pemetrexed carboplatin	18 Years -	AstraZeneca

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