Metastatic Pancreatic Cancer, Pancreatic Cancer
Conditions
Brief summary
This study will compare the anti-tumor efficacy of apricoxib and gemcitabine/erlotinib with placebo and gemcitabine/erlotinib in patients with advanced pancreatic cancer.
Detailed description
This study will compare the anti-tumor efficacy of apricoxib and gemcitabine/erlotinib with placebo and gemcitabine/erlotinib as measured by progression-free survival to test the hypothesis that down regulation of COX-2 and EGFR pathways in patients with up-regulated COX-2 expression in tumors will have a clinical benefit compared with Gemcitabine/Erlotinib only.
Interventions
DRUGgemcitabine
Gemcitabine: per package insert.
DRUGplacebo
placebo: 100 mg tablets, 400 mg/day
DRUGErlotinib
Erlotinib - per package insert.
DRUGapricoxib
apricoxib: 100mg tablets, given orally
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
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas that is locally advanced or metastatic. 2. Life expectancy greater than or equal to 3 months. 3. Patients must have measurable disease by RECIST. 4. ECOG PS of 0, 1, or 2. 5. Negative serum pregnancy test at the time of first dose for women of childbearing potential.
Exclusion criteria
1. Previous chemotherapy as primary treatment for locally advanced or metastatic pancreatic cancer(stage 3 T3 and T4, and all stage 4). 2. RT within 2 weeks or chemotherapy within 3 weeks or noncytotoxic investigational agents within 4 weeks of initiating study treatment. 3. Evidence of New York Heart Association class III or greater cardiac disease. 4. History of myocardial infarction, stroke, ventricular arrhythmia. 5. Symptomatic central nervous system metastases. 6. Pregnant or nursing women. 7. Hypersensitivity or intolerance to apricoxib, erlotinib, gemcitabine, sulfonamides, aspirin, or other non-steroidal anti-inflammatory drugs (NSAIDs). 8. History of upper gastrointestinal bleeding, ulceration or perforation. History of lower GI bleeding, ulceration, or perforation within 12 months. 9. Previous anti-EGFR kinase therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Randomization then every other cycle | Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival | Randomization then every other cycle |
Countries
United States
Participant flow
Recruitment details
Study opened to accrual in August 2008. Enrollment closed on November 2010. One hundred and nine patients were randomized. Patients were recruited from clinical oncology practices.
Participants by arm
| Arm | Count |
|---|---|
| Apricoxib/Gemcitabine/Erlotinib Patients randomized to receive apricoxib + gemcitabine + erlotinib. | 70 |
| Placebo/Gemcitabine/Erlotinib Patients randomized to receive placebo + gemcitabine + erlotinib. | 39 |
| Total | 109 |
Baseline characteristics
| Characteristic | Placebo/Gemcitabine/Erlotinib | Apricoxib/Gemcitabine/Erlotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 32 Participants | 54 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 38 Participants | 55 Participants |
| Age Continuous | 67 years STANDARD_DEVIATION 66 | 63 years STANDARD_DEVIATION 64.2 | 64 years STANDARD_DEVIATION 64.8 |
| Region of Enrollment United States | 39 participants | 70 participants | 109 participants |
| Sex: Female, Male Female | 22 Participants | 41 Participants | 63 Participants |
| Sex: Female, Male Male | 17 Participants | 29 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 70 | 39 / 39 |
| serious Total, serious adverse events | 16 / 70 | 5 / 39 |
Outcome results
Primary
Progression Free Survival
Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.
Time frame: Randomization then 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 0.16 between the proportions of patients who were progression free in AP/EG (0.35) and P/EG (0.19) after 9 months; an overall sample size of approximately 110 patients (73 in AP/EG and 37 in P/EG) was randomized in a 2:1 ratio.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apricoxib/Gemcitabine/Erlotinib | Progression Free Survival | 3.0 Months |
| Placebo/Gemcitabine/Erlotinib | Progression Free Survival | 2.8 Months |
Secondary
Overall Survival
Time frame: Randomization then every other cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apricoxib/Gemcitabine/Erlotinib | Overall Survival | 5.0 Months |
| Placebo/Gemcitabine/Erlotinib | Overall Survival | 4.8 Months |