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).

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pevonedistat; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48187
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Gregory Kalemkerian, M.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): November 4, 2021
• Study Completion (Actual): November 4, 2021

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Pevonedistat
• Other Study ID Numbers: UMCC 2017.063; HUM00131436 (Other Identifier: University of Michigan)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes