Pancreatic Cancer
Conditions
Keywords
capecitabine, oxaliplatin
Brief summary
There are limited treatment options available for patients with advanced pancreatic ductal adenocarcinoma (PDAC). The purpose of this study is to determine the effectiveness and safety of the drugs capecitabine and oxaliplatin in patients who have been diagnosed with advanced and metastatic PDAC treated in the first and second lines.
Detailed description
OBJECTIVES: Primary * To determine the response rate to capecitabine and oxaliplatin in patients with locally advanced or metastatic pancreatic adenocarcinoma Secondary * To determine safety * To determine overall survival * To determine time to progression
Interventions
DRUGCapecitabine
DRUGOxaliplatin
Sponsors
Sanofi
Beth Israel Deaconess Medical 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
* 18 years of age or older * At most one prior chemotherapy regimen for unresectable or metastatic disease. Any adjuvant chemotherapy must have been completed more than 12 months prior to beginning protocol therapy * Histologically or cytologically confirmed adenocarcinoma of the pancreas * At least one measurable lesion according to RECIST criteria that has not been irradiated * Adequate laboratory parameters as outlined in protocol * Anticoagulation with coumadin is permitted, but PT/INR must be monitored closely, given the drug-drug interaction between coumadin and capecitabine * Negative serum pregnancy test within 14 days prior to registration
Exclusion criteria
* Pregnant or lactating women * Life expectancy \< 3 months * Serious, uncontrolled, concurrent infection(s) * Any prior oxaliplatin or fluoropyrimidine therapy * More than one prior chemotherapy regimen for unresectable or metastatic disease * Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil or platinum compounds * Any active second malignancy * Clinically significant cardiac disease or myocardial infarction within the last 12 months * Evidence of CNS metastases or history of uncontrolled seizures, central nervous system disorders or psychiatric disability * Other serious uncontrolled medical conditions * Major surgery within 4 weeks of the start of study treatment, without complete recovery * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * Known, existing uncontrolled coagulopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX. | Response rate (RR) is defined as the proportion of participants achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Response | Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX. | Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria. |
| Overall Survival | Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 10.8 months (95% CI: 7.1-37.7) in this study cohort. | Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods. |
| Progression-Free Survival | Disease evaluations occurred every two cycles (42 days ±2 days) on treatment. In this study cohort, participants were followed for progression up to 38 months. | Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from treatment or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from May 2004 to March 2010.
Participants by arm
| Arm | Count |
|---|---|
| CAPOX Participants self-administered capecitabine 1,000 mg/m2 orally twice daily (total daily dose 2,000 mg/m2), days 1-14 in 21-day cycles. Only 500 mg tablets were used, and doses were rounded to the nearest dose that could be administered with 500 mg tablets. Oxaliplatin 130 mg/m2 was administered intravenously on day 1 every 21 (±2) days. Treatment continued until tumor progression or toxicity requiring discontinuation of therapy. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 24 |
| Overall Study | Poor performance status | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | CAPOX |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 19 Participants |
| Stage Locally Advanced | 2 Participants |
| Stage Metastatic | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 34 / 36 |
| serious Total, serious adverse events | 18 / 36 |
Outcome results
Primary
Response Rate
Response rate (RR) is defined as the proportion of participants achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX.
Population: The analysis dataset is comprised of response evaluable participants which required completion of two cycles of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAPOX | Response Rate | .125 proportion of participants |
Secondary
Best Response
Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria.
Time frame: Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX.
Population: The analysis dataset is comprised of response evaluable participants which required completion of two cycles of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAPOX | Best Response | Complete Response | 0 participants |
| CAPOX | Best Response | Partial Response | 3 participants |
| CAPOX | Best Response | Stable Disease | 13 participants |
| CAPOX | Best Response | Progressive Disease | 8 participants |
Secondary
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Time frame: Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 10.8 months (95% CI: 7.1-37.7) in this study cohort.
Population: The analysis dataset is comprised of treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAPOX | Overall Survival | 7.4 months |
Secondary
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from treatment or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time frame: Disease evaluations occurred every two cycles (42 days ±2 days) on treatment. In this study cohort, participants were followed for progression up to 38 months.
Population: The analysis dataset is comprised of response evaluable participants which required completion of two cycles of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAPOX | Progression-Free Survival | 3.8 months |