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

Study Overview
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Brief Summary
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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).

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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pevonedistat
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pevonedistat plus Docetaxel<br>Pevonedistat 25mg/m2 days 1, 3, 5 Docetaxel 75mg/m2 day 1 21 day cycle | Drug: Pevonedistat<br>* 25mg/m2 days 1, 3, 5<br>* Other names: TAK-924;Drug: Docetaxel<br>* 75mg/m2 day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients That Respond to Treatment | Response is defined as either Partial Response or Complete Response. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions. Complete Response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival Time | Progression-free survival is defined as the duration of time from start of treatment to time of progression. Progressive Disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. | Up to 2 Years | 
| Median Overall Survival Time | Overall survival is defined as the duration of time from start of treatment to time of passing. | Up to 2 Years | 
| The Number of Patients Who Achieve Stable Disease | Stable disease rate will be reported as the count and proportion of patients who achieve stable disease. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started. | Up to 2 Years | 
| The Number of Toxicities by System Organ Class | All recorded toxicities will be listed and tabulated by system organ class. The NCI CTCAE version 4.03 will be utilized for AE reporting. | up to 30 days post last study drug dose, patients were allowed to stay on study drug treatment until progression. Data was collected over 3.5 years. |