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

• Status: Terminated
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Adavosertib; Carboplatin; Pemetrexed

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