Clinical trial NCT02087241: Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Previously Untreated Stage IV Non-Squamous Non Small Cell Lung Cancer
Keywords: Stage IV Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-03-14
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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).

Eligibility criteria: Inclusion Criteria

* Provision of informed consent prior to any study specific procedures
* Histologic or cytologic diagnosis of advanced NSCLC, Recurrent or Stage IV disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).
* No prior chemotherapy for locally advanced or metastatic disease
* Subjects with a known EGFR mutation must have received previous treatment with an EGFR tyrosine kinase inhibitor; and subjects with a known ALK translocation must have received previous treatment with an ALK inhibitor.
* No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area.
* At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
* Mandatory availability of tumour tissue (archival or fresh if archival is not available) for TP53 determination.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
* Absolute neutrophil count (ANC) ≥1500/μL
* Hemoglobin (Hgb) ≥10 g/dL
* Platelets ≥100,000/μL
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases
* Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease
* Serum creatinine ≤1.5 x ULN and a calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method
* 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 who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment
* Predicted life expectancy ≥12 weeks
* Must be ≥18 years of age
* Willingness and ability to comply with study and follow-up procedures
* Ability to understand the nature of this trial and give written informed consent Exclusion criteria
* Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775
* Major surgical procedures ≤28 days of beginning AZD1775, or minor surgical procedures ≤7 days
* Known central nervous system (CNS) disease
* Subject has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates
* Any known hypersensitivity or contraindication to the components of study treatment
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (\[NYHA\] Appendix G) ≥ Class 2
* Corrected QT interval (QTc) \>470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndrome.
* Pregnant or lactating
* Any serious, active underlying medical condition that would impair the ability of the subjects to receive study treatment
* Unable or unwilling to take folic acid or vitamin B12
* 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

Primary outcomes:
measure: Progression Free Survival
timeFrame: 6 months
Secondary outcomes:
measure: Assess the Objective Response Rates in Each Arm
timeFrame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
measure: Assess the Disease Control Rate in Each Treatment Arm
timeFrame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
measure: Assess the Duration of Response in Each Treatment Arm
timeFrame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
measure: Assess Overall Survival in Each Treatment Arm
timeFrame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Other outcomes:
Locations:
city: Englewood
country: United States
facility: Research Site
state: Colorado
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David R Spigel, MD
role: PRINCIPAL_INVESTIGATOR
References: