Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer
Condition: Previously Untreated Stage IV Non-Squamous Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: AZD1775; AZD1775 Matching Placebo; pemetrexed; carboplatin
Intervention description: 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 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; 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.; 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.
Intervention MeSH terms: Carboplatin; Pemetrexed; Adavosertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage IV Lung Cancer

Summary:

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

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