Ductal Adenocarcinoma of Pancreas, Adenocarcinoma of Ampulla
Conditions
Brief summary
Patients diagnosed with pancreatic cancer without clinically detectable metastatic disease will be treated with standardized systemic chemotherapy, followed by chemoradiation, and then surgical resection for those with resectable or borderline resectable disease. The primary endpoint is disease-free survival at 1 yr from initiation of treatment.
Detailed description
Patients with ductal adenocarcinoma of the pancreas (or ampulla) that have received no prior therapy and have no clinically detectable metastatic disease will be enrolled. Management will be driven by resectability status as defined by the American College of Surgeons. All patients will be defined at entry as Resectable, Borderline Resectable or Locally Advanced (Unresectable). All patients will be treated initially with gemcitabine and nanoparticle albumin bound paclitaxel (nab-paclitaxel) every 14 days for 4 cycles. Patients classified as Resectable, who have CA19-9 below 180 and CA-125 below 30 will then proceed to resection. All other patients will get 5-fluorouracil as 46 hr infusion given with leucovorin and irinotecan (FOLFIRI-3) every 14 days x 4 cycles. All patients without progression will then receive chemoradiation consisting of external beam radiotherapy (40 Gy in 20 fractions given over 4 weeks). During radiation all patients will receive radiosensitizing radiotherapy as: 5-fluorouracil at 225 mg/m2 5 days per week, Mitomycin-C at 3 mg.m2 on d1, 8, 15 & 22; Cisplatin at 10 mg/m2 on d2, 9, 16, 23 and unfractionated heparin at 6,000 units/m2 daily in divided doses from day 1 to day 28. After approximately 4 weeks to recover from chemoradiation, all patients with Resectable or Borderline Resectable disease will undergo definitive surgery. Adjuvant therapy with FOLFIR-3 for an additional 6 cycles will be offered to all patients post-operatively. Patients will then be actively followed every 3 to 6 months in keeping with National Comprehensive Cancer Network (NCCN) guidelines for 2 yrs, and then followed for recurrence, late toxicity and vital status every 6 months through 5 years.
Interventions
DRUGGemcitabine and nanoparticle albumin bound paclitaxel
Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles
DRUG5-fluorouracil and irinotecan
FOLFIRI.3 given every 14 days x 4 cycles
RADIATIONPreoperative chemoradiation
Pre-operative chemoradiation to 40 Gy in 20 fractions
PROCEDUREDefinitive resection
Definitive surgical resection of primary tumor
Sponsors
Essentia Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Histologic proof of adenocarcinoma consistent with ductal carcinoma of pancreas or ampulla, with no evidence of metastatic disease by clinical exam or cross-sectional imaging. * Fitness for chemotherapy in judgement of treating physician * Bilirubin \< 4 (any means of biliary drainage acceptable)
Exclusion criteria
* Medical or mental illness precluding provision of informed consent * Pregnancy * Active infection for which neutropenia would pose high risk of mortality
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Free Survival | 1 yr form onset of treatment | Percentage of patients alive and free of detectable disease 1 yr from start of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R-0 Rate | Time of surgery | Rate of patients having surgery who have negative surgical margins (i.e. R-0 resection) |
| Overall Survival | Up to 3 years from registration | Time to death from any cause measured from start of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Resectable, Low Risk Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy.
Gemcitabine and nanoparticle albumin bound paclitaxel: Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles
Definitive resection: Definitive surgical resection of primary tumor | 1 |
| Locally Advanced Systemic chemotherapy followed by chemoradiation, followed by definitive surgery
Gemcitabine and nanoparticle albumin bound paclitaxel: Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles
5-fluorouracil and irinotecan: FOLFIRI.3 given every 14 days x 4 cycles
Preoperative chemoradiation: Pre-operative chemoradiation to 40 Gy in 20 fractions
Definitive resection: Definitive surgical resection of primary tumor | 10 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Did not start protocol therapy | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Study terminated | 0 | 1 |
Baseline characteristics
| Characteristic | Locally Advanced | Total | Resectable, Low Risk |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 8 Participants | 1 Participants |
| Age, Continuous | 63 years | 63 years | 64 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 10 participants | 11 participants | 1 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 10 |
| other Total, other adverse events | 0 / 1 | 2 / 10 |
| serious Total, serious adverse events | 0 / 1 | 3 / 10 |
Outcome results
Primary
Relapse Free Survival
Percentage of patients alive and free of detectable disease 1 yr from start of treatment
Time frame: 1 yr form onset of treatment
Population: Due to excessive toxicity of study regimen, the study was permanently closed prior to data analysis.
Secondary
Overall Survival
Time to death from any cause measured from start of treatment
Time frame: Up to 3 years from registration
Population: Data not collected, study terminated
Secondary
R-0 Rate
Rate of patients having surgery who have negative surgical margins (i.e. R-0 resection)
Time frame: Time of surgery
Population: Data not collected, study Terminated