Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

Phase II Trial of Pevonedistat (TAK-924) Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

This study is a single institution Phase II single arm trial to assess the efficacy of the combination of pevonedistat plus docetaxel in patients with previously treated advanced NSCLC (non-small cell lung cancer).

Inclusion Criteria:

• Patients 18 years of age or older
• Histologically confirmed stage IV NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, or not otherwise specified) or recurrent NSCLC not amenable to curative therapy
• Patients must have already received platinum-based chemotherapy; they may have also received prior immunotherapy or targeted therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
• Clinical laboratory values within appropriate parameters
• Female patients who are of childbearing potential and all males must agree to practice true abstinence or use effective methods of contraception
• Patients must be able to understand and sign the informed consent.
• Patients must have measurable disease as defined by RECIST v1.1 criteria
• It is preferable that patients have an adequate tissue sample available

Exclusion Criteria:

• Treatment with any investigational products within 4 weeks before the first dose of any study drug
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures
• Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia that require IV antibiotics within 2 weeks of starting study treatment
• Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period
• Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Life-threatening illness unrelated to cancer
• Patients with uncontrolled coagulopathy or bleeding disorder
• Known human immunodeficiency virus (HIV) seropositivity
• Known hepatitis B surface antigen seropositivity or known or suspected active hepatitis C infection
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiopulmonary disease
• Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
• Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines
• Interstitial lung disease or pulmonary fibrosis
• Systemic antineoplastic therapy or radiotherapy for other malignant conditions within 14 days before the first dose of any study drug, except for hydroxyurea.
• Symptomatic or history of untreated brain or leptomeningeal metastases. Treated patients should be neurologically stable for 4 weeks after completion of appropriate therapy. Patients should be off steroids at least 3 days prior to start of therapy on clinical trial.
• Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug. Clinically significant metabolic enzyme inducers are not permitted during this study (see Appendix III for more details).
• Female patients who are lactating, breastfeeding, or have a positive pregnancy test
• Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
• Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
• Known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
• Prior therapy with docetaxel for non-small cell lung cancer
• Peripheral neuropathy of CTCAE v4.03 grade ≥ 2