Pancreatic Carcinoma
Conditions
Keywords
Pancreatic, Periampullary Cancer, Preoperative Biliary Drainage, Resectable
Brief summary
The purpose of this study is to demonstrate that preoperative biliary drainage using self-expanding metal stents (SEMS) does not negatively impact overall surgical outcomes in patients undergoing pancreaticoduodenectomy for treatment of pancreatic or periampullary cancer.
Interventions
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Willing and able to comply with the study procedures and provide written informed consent to participate in the study * Diagnosis of probable pancreatic cancer, distal common bile duct (CBD) cholangiocarcinoma and other periampullary cancers (histology not required) * Biliary obstructive symptoms or signs * Bilirubin level at/above 100 umol per liter (5.8 mg/dL) * Distal biliary obstruction consistent with pancreatic cancer, distal CBD cholangiocarcinoma or other periampullary malignancy * Location of distal biliary obstruction is such that it would allow the proximal end of a stent to be positioned at least 2cm from the hilum * Patients deemed as resectable by pancreatic protocol CT or MRI * Surgical candidate per pancreatobiliary surgeon after multi-disciplinary discussion * Surgery intent within 4 weeks * Endoscopic and surgical treatment to be provided by same team
Exclusion criteria
* Biliary strictures caused by confirmed benign tumors * Biliary strictures caused by malignancies other than pancreatic cancer, distal CBD cholangiocarcinoma and other periampullary cancers * Surgically altered biliary tract anatomy, not including prior cholecystectomy * Neoadjuvant chemotherapy for current malignancy * Palliative indication due to reasons other than surgical candidate status * Previous biliary drainage by ERCP/PTC * Patients for whom endoscopic techniques are contraindicated * Participation in another investigational trial within 90 days * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Pre-operative, Operative and Post-operative Adverse Events to 120 Days Post Randomization or to 30 Days Post Surgery, Whichever Comes Last | 120 to 150 days | The primary end point was all serious adverse events (SAEs), including all preoperative, operative and postoperative adverse events reported from the time of randomization to 120 days post-randomization or 30 days post-CIS (up to 150 days post-randomization), whichever occurred later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stent Placement Success | Procedure | Stent placement success: ability to deploy the stent in satisfactory position across the stricture (For patients who are randomized to biliary drainage with a metal stent) |
| Number of Patients With Biliary Re-interventions | 120 to 150 days | Count of patients with biliary interventions after baseline |
| Success Rate of Curative Intent Surgery | 4 weeks | This is the number of patients that had successful resection |
| All-cause Mortality | 150 days | Mortality which occurs within 150 days of baseline |
Countries
Australia, Belgium, China, France, Hong Kong, India, Italy, Japan, United States
Participant flow
Recruitment details
Study participants were screened by site investigators at 11 academic medical centers globally between February 2013 and August 2021. The first participant was enrolled in February 2013 and the last participant was enrolled in August 2021.
Pre-assignment details
Of the 765 participants assessed for eligibility, 284 met criteria and were randomized.
Participants by arm
| Arm | Count |
|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System Patients in this group will receive a fully covered or uncovered study SEMS (self-expanding metal stent)
WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | 144 |
| None (No Pre-Operative Biliary Drainage) Patients in this group will not receive pre-operative biliary drainage with a study SEMS | 140 |
| Total | 284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | No longer meets protocol criteria | 2 | 0 |
| Overall Study | Patient refused surgery | 1 | 1 |
| Overall Study | Surgery delayed > 120 days | 1 | 0 |
| Overall Study | Unable to implant study device | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | None (No Pre-Operative Biliary Drainage) | Total | WallFlex™ Biliary RX Fully Covered/Uncovered Stent System |
|---|---|---|---|
| Age, Continuous | 64.9 Years STANDARD_DEVIATION 11.7 | 63.4 Years STANDARD_DEVIATION 11.7 | 61.9 Years STANDARD_DEVIATION 11.5 |
| BMI | 24.1 kg/m^2 STANDARD_DEVIATION 3.9 | 24.2 kg/m^2 STANDARD_DEVIATION 3.9 | 24.3 kg/m^2 STANDARD_DEVIATION 3.9 |
| Height | 161.8 cm STANDARD_DEVIATION 8.7 | 162.5 cm STANDARD_DEVIATION 8.9 | 163.3 cm STANDARD_DEVIATION 9.1 |
| Karnofsky Score (overall health status) | 89.6 units on a scale STANDARD_DEVIATION 9.1 | 90.5 units on a scale STANDARD_DEVIATION 8.2 | 91.3 units on a scale STANDARD_DEVIATION 7.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Australia | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Belgium | 7 participants | 15 participants | 8 participants |
| Region of Enrollment China | 2 participants | 4 participants | 2 participants |
| Region of Enrollment France | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Hong Kong | 51 participants | 103 participants | 52 participants |
| Region of Enrollment India | 37 participants | 73 participants | 36 participants |
| Region of Enrollment Italy | 27 participants | 54 participants | 27 participants |
| Region of Enrollment Japan | 7 participants | 16 participants | 9 participants |
| Region of Enrollment United States | 3 participants | 7 participants | 4 participants |
| Sex: Female, Male Female | 59 Participants | 123 Participants | 64 Participants |
| Sex: Female, Male Male | 81 Participants | 161 Participants | 80 Participants |
| Total serum bilirubin | 12.9 mg/dl STANDARD_DEVIATION 5 | 13.4 mg/dl STANDARD_DEVIATION 5.7 | 14.0 mg/dl STANDARD_DEVIATION 6.3 |
| Tumor location on imaging Ampullary | 34 Participants | 64 Participants | 30 Participants |
| Tumor location on imaging distal | 16 Participants | 28 Participants | 12 Participants |
| Tumor location on imaging Duodenum | 1 Participants | 1 Participants | 0 Participants |
| Tumor location on imaging Head | 85 Participants | 187 Participants | 102 Participants |
| Tumor location on imaging Isthmus | 1 Participants | 1 Participants | 0 Participants |
| Tumor location on imaging tail | 1 Participants | 1 Participants | 0 Participants |
| Tumor location on imaging Uncinate process | 2 Participants | 2 Participants | 0 Participants |
| Weight | 63.2 kg STANDARD_DEVIATION 12.7 | 64.1 kg STANDARD_DEVIATION 12.8 | 65.0 kg STANDARD_DEVIATION 12.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 144 | 11 / 140 |
| other Total, other adverse events | 0 / 144 | 0 / 140 |
| serious Total, serious adverse events | 40 / 144 | 36 / 140 |
Outcome results
Primary
Number of Serious Pre-operative, Operative and Post-operative Adverse Events to 120 Days Post Randomization or to 30 Days Post Surgery, Whichever Comes Last
The primary end point was all serious adverse events (SAEs), including all preoperative, operative and postoperative adverse events reported from the time of randomization to 120 days post-randomization or 30 days post-CIS (up to 150 days post-randomization), whichever occurred later.
Time frame: 120 to 150 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | Number of Serious Pre-operative, Operative and Post-operative Adverse Events to 120 Days Post Randomization or to 30 Days Post Surgery, Whichever Comes Last | 40 Participants |
| None (No Pre-Operative Biliary Drainage) | Number of Serious Pre-operative, Operative and Post-operative Adverse Events to 120 Days Post Randomization or to 30 Days Post Surgery, Whichever Comes Last | 36 Participants |
Secondary
All-cause Mortality
Mortality which occurs within 150 days of baseline
Time frame: 150 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | All-cause Mortality | 11 Participants |
| None (No Pre-Operative Biliary Drainage) | All-cause Mortality | 11 Participants |
Secondary
Number of Patients With Biliary Re-interventions
Count of patients with biliary interventions after baseline
Time frame: 120 to 150 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | Number of Patients With Biliary Re-interventions | 8 Participants |
| None (No Pre-Operative Biliary Drainage) | Number of Patients With Biliary Re-interventions | 12 Participants |
Secondary
Stent Placement Success
Stent placement success: ability to deploy the stent in satisfactory position across the stricture (For patients who are randomized to biliary drainage with a metal stent)
Time frame: Procedure
Population: 3 patients in the WallFlex Biliary RX Fully Covered/Uncovered Stent arm had no stent placed. Patients in the no drainage arm are not intended to have a stent placement per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | Stent Placement Success | 140 Participants |
Secondary
Success Rate of Curative Intent Surgery
This is the number of patients that had successful resection
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex™ Biliary RX Fully Covered/Uncovered Stent System | Success Rate of Curative Intent Surgery | 103 Participants |
| None (No Pre-Operative Biliary Drainage) | Success Rate of Curative Intent Surgery | 115 Participants |