Pancreatic Cancer
Conditions
Keywords
Pancreatic cancer, Dasatinib, chemotherapy, Locally advanced
Brief summary
The purpose of this study is to determine whether patients with locally advanced pancreatic cancer who receive dasatinib added to standard of care (gemcitabine) live longer, compared to patients who receive standard of care (gemcitabine) plus placebo; i.e. gemcitabine alone.
Interventions
DRUGdasatinib
GEM 1000 mg/m2 by intravenous \[IV\] infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg (or matched placebo) by mouth once daily (QD). Subjects will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
DRUGPlacebo
Matching Placebo
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic documentation of unresectable adenocarcinoma of the pancreas. * Recovery from toxicity of previous procedures to establish the diagnosis. ECOG PS 0 or 1. * Adequate organ function.
Exclusion criteria
* Evidence of metastatic disease. * Previous radiotherapy or chemoradiotherapy. * History of or current pleural effusion. * History of significant cardiovascular disease. * Clinically significant bleeding disorder or coagulopathy. * Concomitant medication with strong CYP 3A4 inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization until date of death from any cause by 02 December 2013 | Overall survival (OS) is the time from randomization until time of death from any cause by 02 December 2013. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Time from randomization to earliest PFS event by 02 December 2013 | PFS - time from randomization to unequivocal local or distant disease progression, death or discontinuation from trial for any reason by 02 December 2013. Progression events were determined according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 every 8 weeks. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Ireland, Italy, Poland, Romania, Russia, United Kingdom, United States
Participant flow
Recruitment details
202 participants were enrolled at 79 study sites in 15 countries.
Pre-assignment details
Participants were randomly assigned in a 1:1 ratio to receive dasatinib + gemcitabine (GEM) or placebo + GEM. Participants were stratified at the time of randomization by baseline Eastern Cooperative Oncology Group performance status (ECOG PS) (0 versus 1) and intent to receive radiotherapy (RT) (yes or no).
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib + GEM GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus dasatinib 100 mg by mouth QD. | 100 |
| Placebo + GEM GEM 1000 mg/m2 by IV infusion weekly for 3 weeks of a 4-week cycle plus matched placebo by mouth QD. | 102 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 12 |
| Overall Study | Death | 4 | 3 |
| Overall Study | Disease progression | 42 | 58 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 11 | 15 |
| Overall Study | Protocol deviation | 1 | 2 |
| Overall Study | Sponsor discontinued study | 1 | 4 |
| Overall Study | Withdrawal by Subject | 14 | 8 |
Baseline characteristics
| Characteristic | Dasatinib + GEM | Placebo + GEM | Total |
|---|---|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 9.1 | 64.7 Years STANDARD_DEVIATION 9.6 | 64.8 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 43 Participants | 56 Participants | 99 Participants |
| Sex: Female, Male Male | 57 Participants | 46 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / 98 | 98 / 101 |
| serious Total, serious adverse events | 53 / 98 | 48 / 101 |
Outcome results
Primary
Overall Survival
Overall survival (OS) is the time from randomization until time of death from any cause by 02 December 2013.
Time frame: From randomization until date of death from any cause by 02 December 2013
Population: The intent-to-treat (ITT) data which was composed of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib + GEM | Overall Survival | 375 Days |
| Placebo + GEM | Overall Survival | 393 Days |
Comparison: Using a 1-sided alpha=0.2, a population of 200 participants (100 GEM plus dasatinib and 100 GEM plus placebo) has 79% power to show an increase in median OS from 10 to 13.3 months (hazard ratio \[HR\] =0.75, assuming analysis of 135 deaths).p-value: 0.386495% CI: [0.85, 1.65]Cox proportional hazard model
Secondary
Progression Free Survival (PFS)
PFS - time from randomization to unequivocal local or distant disease progression, death or discontinuation from trial for any reason by 02 December 2013. Progression events were determined according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 every 8 weeks.
Time frame: Time from randomization to earliest PFS event by 02 December 2013
Population: The ITT data which was composed of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib + GEM | Progression Free Survival (PFS) | 167 Days |
| Placebo + GEM | Progression Free Survival (PFS) | 166 Days |
Comparison: Trial has 88% power to show a median PFS increase from 5 to 7 months (with 1-sided alpha=0.15, total 176 events, HR=0.714).p-value: 0.676195% CI: [0.73, 1.34]Cox proportional hazard model