Non-small Cell Lung Cancer
Conditions
Keywords
Advanced stage
Brief summary
The purpose of this study is to determine the efficacy and the toxicities of the study drug PD0332991 in the treatment of patients with Stage IV non-small cell lung cancer with wildtype retinoblastoma protein (RB) and inactivated cyclin dependent kinase (CDK) N2A in the tumor.
Detailed description
The oral drug PD0332991 is a highly selective reversible inhibitor of cyclin-dependent kinases 4 & 6 that is being studied for use in the treatment of advanced non-small cell lung cancer.
Interventions
DRUGPD0332991
PD0332991 125 mg PO days 1 - 21
Sponsors
University of Florida
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
* Histologically or cytologically proven non small cell lung cancer * Stage IV (M1a or M1b) disease. Patients may also have recurrence of early-stage disease or locally advanced disease with the presence of new distant metastases. * Cyclin dependent kinase (CDK)N2a (p16) protein absent or expressed at a low level in tumor biopsy specimen * Failed or intolerant of at least one prior systemic chemotherapy regimen (there is no maximum number of prior chemotherapy regimens) * Eastern cooperative oncology group (ECOG) performance status 0-2 * Age \>18 years. * Adequate organ and bone marrow function * Measurable disease by standard RECIST v1.1 criteria * Life expectancy of greater than 3 months
Exclusion criteria
* Inability to understand or sign the informed consent document * Inability or unwillingness to take oral medications * No available tissue specimen for p16 analysis * Chemotherapy or radiotherapy within 3 weeks prior to beginning the study drug * Other investigational agents within 4 weeks prior to beginning the study drug * All side effects from previous chemotherapy, radiotherapy or investigational agents not resolved, returned to baseline or returned to Grade 1 toxicity (exceptions are grade 2 alopecia and grade 2 peripheral neuropathy) * Major surgery within 4 weeks prior to beginning the study drug * Surgical scar from previous surgery not healed prior to beginning the study drug * High-dose or chronic steroid use * High-dose statins within 7 days * History of rhabdomyolysis * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, stroke or myocardial infarction within 3 months, or psychiatric illness/social situations that would limit compliance with study requirements. * Baseline corrected QT interval (QTc) \>470ms * Pre-existing clinically significant cardiac, hepatic or renal dysfunction at the discretion of the treating physician * Untreated or uncontrolled (symptomatic or asymptomatic) brain metastases * Leptomeningeal carcinomatosis * Inability or unwillingness to use contraception during the treatment period by patients with reproductive potential. * Pregnant or breastfeeding women * HIV-positive patients on combination antiretroviral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response by Direct RECIST Measurement | 6 months | Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 14 months | Median overall survival |
| Progression-free Survival | 12 months | Median progression-free survival. |
| Plasma Levels | 6 months | Plasma levels of p16, phosphorylated RB and cyclin d1 in blood. |
| Grade of Study Drug Toxicity | 24 months | The number of all toxicities and grades 3 and 4 (per CTCAE v3.0) toxicities that occured during the administration of the drug and during the follow up period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PD0332991 PD0332991 125 mg PO days 1 - 21
PD0332991: PD0332991 125 mg PO days 1 - 21 | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | PD0332991 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
Tumor Response by Direct RECIST Measurement
Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PD0332991 | Tumor Response by Direct RECIST Measurement | 0 participants |
Secondary
Grade of Study Drug Toxicity
The number of all toxicities and grades 3 and 4 (per CTCAE v3.0) toxicities that occured during the administration of the drug and during the follow up period.
Time frame: 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PD0332991 | Grade of Study Drug Toxicity | Grade 3 and 4 Toxicities | 9 Events |
| PD0332991 | Grade of Study Drug Toxicity | All Toxicities (Grades 1 - 5) | 86 Events |
Secondary
Overall Survival
Median overall survival
Time frame: 14 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| PD0332991 | Overall Survival | 20.3 weeks | Standard Error 1.7 |
Secondary
Plasma Levels
Plasma levels of p16, phosphorylated RB and cyclin d1 in blood.
Time frame: 6 months
Population: 4 of the 16 samples were tested by protein immunoblot (Western blot), and due to the test not being sensitive enough to detect p16, phosphorylated RB or cyclin D1 protein bands in any of the samples, the decision was made not to purse this testing any further.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PD0332991 | Plasma Levels | NA Arbitrary Units |
Secondary
Progression-free Survival
Median progression-free survival.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| PD0332991 | Progression-free Survival | 8 Weeks | Standard Error 0.7 |