Recurrent Non Small Cell Lung Cancer
Conditions
Brief summary
This study will compare the anti-tumor efficacy of apricoxib and erlotinib with placebo and erlotinib as measured by time to disease progression to test the hypothesis that down regulation of COX-2 and EGFR pathways in patients with up-regulated COX-2 expression in tumor will have a clinical benefit compared with erlotinib alone.
Interventions
DRUGapricoxib/erlotinib
apricoxib: 100 mg tablets, 400mg/day erlotinib: per package insert
DRUGerlotinib/placebo
erlotinib: per package insert placebo: 100 mg tablets, 400 mg/day
Sponsors
Tragara Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically determined Stage IV NSCLC including Stage IIIb (pleural effusion) * Failed at least one prior platinum-based chemotherapy for Stage IIIb or Stage IV NSCLC. Patients receiving platinum-based chemotherapy only given in an adjuvant setting are not eligible. * Measurable disease by RECIST * Greater than or equal to 18 years of age * ECOG PS of 0 or 1
Exclusion criteria
* Radiation therapy within 2 weeks; chemotherapy within 3 weeks; non-cytotoxic investigational agents within 4 weeks of initiating study treatment * Evidence of NYHA class III or greater cardiac disease * History of MI, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months * Known HIV infection or AIDS * Symptomatic CNS metastases * Pregnant or nursing women * Hypersensitivity or intolerance to erlotinib, sulfonamides, aspirin, or other NSAIDs. * History of upper GI bleeding, ulceration, or perforation * Prior history of COX-2 inhibitor therapy for the treatment of metastatic NSCLC * Previous anti-EGFR kinase therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to Disease Progression (TDP) | Baseline and every other cycle. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival | Randomization and every cycle |
Countries
United States
Participant flow
Recruitment details
The study opened to accural in April 2008. Enrollment closed in May 2010. One hundred seventy six patients were enrolled with 120 patients randomized. Patients were recruited from clinical oncology practices.
Pre-assignment details
Enrolled patients underwent a 5-day open label treatment with apricoxib to determine the maximum suppression of PGEM from a baseline measurment. PGEM was used as a biomarker of COX-2 activity in the tumor. Patients with at least a 50% decrease on day 5 from their baseline measurment were eligible to be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Apricoxib/Erlotinib Patients randomized to receive apricoxib and erlotinib. | 78 |
| Placebo/Erlotinib Patients randomized to receive placebo and erlotinib. | 42 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Had not progressed. | 4 | 3 |
Baseline characteristics
| Characteristic | Placebo/Erlotinib | Apricoxib/Erlotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 32 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 46 Participants | 69 Participants |
| Age Continuous | 64.6 years STANDARD_DEVIATION 11.16 | 62.1 years STANDARD_DEVIATION 10.78 | 62.9 years STANDARD_DEVIATION 10.94 |
| Region of Enrollment United States | 42 participants | 78 participants | 120 participants |
| Sex: Female, Male Female | 17 Participants | 36 Participants | 53 Participants |
| Sex: Female, Male Male | 25 Participants | 42 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 78 | 42 / 42 |
| serious Total, serious adverse events | 13 / 78 | 4 / 42 |
Outcome results
Primary
Time to Disease Progression (TDP)
Time frame: Baseline and every other cycle.
Population: A 1-sided log rank test was used to achieve 80% power at an α=0.20 significance level to detect a difference of 0.13 between the proportions of patients who are progression free in AP/E (0.34) and P/E (0.21) after 5 months; an overall sample size of 115 patients (77 in AP/E and 38 in P/E) will be randomized in a 2:1 ratio in this study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apricoxib/Erlotinib | Time to Disease Progression (TDP) | 1.80 months |
| Placebo/Erlotinib | Time to Disease Progression (TDP) | 2.10 months |
Secondary
Overall Survival
Time frame: Randomization and every cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apricoxib/Erlotinib | Overall Survival | 5.90 months |
| Placebo/Erlotinib | Overall Survival | 5.60 months |