Non-small Cell Lung Cancer
Conditions
Brief summary
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).
Interventions
DRUGPevonedistat
25mg/m2 days 1, 3, 5
DRUGDocetaxel
75mg/m2 day 1
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients That Respond to Treatment | Up to 2 Years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival Time | Up to 2 Years | 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. |
| Median Overall Survival Time | Up to 2 Years | Overall survival is defined as the duration of time from start of treatment to time of passing. |
| The Number of Patients Who Achieve Stable Disease | Up to 2 Years | 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. |
| The Number of Toxicities by System Organ Class | 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. | All recorded toxicities will be listed and tabulated by system organ class. The NCI CTCAE version 4.03 will be utilized for AE reporting. |
Countries
United States
Participant flow
Pre-assignment details
9 patients screen failed
Participants by arm
| Arm | Count |
|---|---|
| Pevonedistat Plus Docetaxel Pevonedistat 25mg/m2 days 1, 3, 5 Docetaxel 75mg/m2 day 1 21 day cycle
Pevonedistat: 25mg/m2 days 1, 3, 5
Docetaxel: 75mg/m2 day 1 | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient never started treatment | 1 |
Baseline characteristics
| Characteristic | Pevonedistat Plus Docetaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 12 / 30 |
Outcome results
Primary
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.
Time frame: Up to 2 Years
Population: 27 patients participated in the trial long enough to be considered evaluable for this outcome measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pevonedistat Plus Docetaxel | The Percentage of Patients That Respond to Treatment | 22 percent of participants |
Secondary
Median Overall Survival Time
Overall survival is defined as the duration of time from start of treatment to time of passing.
Time frame: Up to 2 Years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pevonedistat Plus Docetaxel | Median Overall Survival Time | 397 days |
Secondary
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.
Time frame: Up to 2 Years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pevonedistat Plus Docetaxel | Median Progression Free Survival Time | 124 days |
Secondary
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.
Time frame: Up to 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pevonedistat Plus Docetaxel | The Number of Patients Who Achieve Stable Disease | 12 Participants |
Secondary
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.
Time frame: 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.
Population: Percentage of Grade 3-5 Adverse Events classified according to the Row Titles. The investigations group represents adverse events due to treatment drugs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | Blood and Lymphatic system disorders- grade 3 | 10 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | Gastrointestinal disorders- grade 3 | 6.7 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | General disorders and administration site conditions- grade 3 | 10 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | hepatobiliary disorders- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | infections and infestations- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | infections and infestations- grade 4 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | investigations- grade 3 | 16.7 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | investigations- grade 4 | 13.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | metabolism and nutrition disorders- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | nervous system disorders- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | respiratory, thoracic and mediastinal disorders- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |
| Pevonedistat Plus Docetaxel | The Number of Toxicities by System Organ Class | Skin and subcutaneous tissue disorders- grade 3 | 3.3 percentage of Grade 3-5 Adverse Events |