Resectable Pancreatic Cancers
Conditions
Keywords
Cancer of the pancreas
Brief summary
This research protocol will evaluate the feasibility of administering neoadjuvant gemcitabine and nab-paclitaxel with hypofractionated, image guided, intensity modulated radiotherapy (HIGRT) in resectable and borderline resectable pancreatic cancer
Detailed description
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and accounts for roughly 40,000 deaths each year. Despite the use of neoadjuvant and adjuvant therapies, little progress has been made in the the last three decades, and the search for more efficacious treatment continues.In patients with a good performance status the combination of effective systemic therapy with gemcitabine/nab-paclitaxel and high dose local radiotherapy may improve disease outcomes. This is a prospective, single arm study in patients in newly diagnosed, previously untreated pancreatic cancer who are planned to undergo surgical resection The primary objective of this study is to evaluate the toxicity of a neoadjuvant approach incorporating gemcitabine/nab-paclitaxel and Hypofractionated image guided intensity-modulated radiotherapy (HIGRT) prior to surgical resection. Eligible subjects will recieve standard neoadjuvant gemcitabine and nab-paclitaxel dosing is as follows:Nab-Paclitaxel (125mg/m2) days 1,8,15 every 28 days for 2 cycles Gemcitabine (1000mg/m2) days 1,8,15 every 28 days for 2 cycles followed by HIGRT and surgical resection. Adjuvant chemotherapy may be given post surgery at the discretion of the treating medical oncologist.
Interventions
Prospective, single arm study ; eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel. All chemotherapy administered to study subjects is standard of care. The chemotherapy combination, gemcitabine/nab-paclitaxel, is considered to be a standard-of-care, non-investigational chemotherapy combination; chemotherapy dosing and treatment schedule will be managed by the treating medical oncologist. Restaging will be completed post chemotherapy.
RADIATIONRadiation therapy
5 fractions of hypofractionated IGRT or IMRT at 5Gy per fraction will be delivered before surgery. Restaging will be completed post radiation therapy.
OTHERSugical resection
Surgical resection of the pancreas post radiation therapy
Adjuvant chemotherapy may be given after surgery at the clinical discretion of the medical oncologist
Sponsors
Duke University
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
1. Patient has signed informed consent and is willing to comply with the protocol 2. Histologically or cytologically proven adenocarcinoma of the pancreas (within the last 90 days) 3. Either resectable or borderline resectable as determined on staging imaging (as defined by National Comprehensive Cancer Network \[NCCN\]) 4. Patient is 18 years or older 5. Karnofsky performance status 70 or greater 6. The ANC count ≥ 1500, the platelet count ≥ 100,000 and hemoglobin ≥ 9g/dL 7. Laboratory values meet the following constraints: Bilirubin less than or equal to 2 mg/dL; AST and ALT less than or equal to 3 x ULN (stenting to improve biliary obstruction is permitted) 8. No evidence of metastatic disease based on imaging of the chest, abdomen and pelvis.
Exclusion criteria
1. Metastatic disease on pretreatment imaging 2. Prior systemic therapy 3. Prior abdominal radiation. Any prior radiation must be approved by the Radiation Oncology PI 4. Previous treatment for pancreatic cancer 5. Patients with any serious/poorly controlled medical or psychological conditions that would be exacerbated by treatment, would complicate protocol compliance 6. Pregnant or lactating. Adequate birth control must be used if of child bearing potential per institutional policy. Negative pregnancy test in female patients of child-bearing potential per institutional policy. Post-menopausal women must have had amenorrhea for at least 18 months to be considered non-child bearing 7. Clinically significant peripheral vascular disease 8. Presence of active or chronic infection 9. Clinically significant atherosclerotic cardiovascular disease including patients with New York Heart Class II/III/IV CHF, ventricular arrhythmias requiring medication, myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary artery bypass grafting, angioplasty, cardiac or other vascular stenting within the past 6 months 10. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within six months prior to treatment start 11. History of collagen vascular disease or inflammatory bowel disease (Crohn's or ulcerative colitis) 12. Current grade 2 or higher peripheral neuropathy 13. Anticoagulation with warfarin 14. History of arterial thromboembolic events or symptomatic pulmonary embolism within the past 6 months 15. Active bleeding diathesis or history of major bleeding, CNS bleeding, or significant hemoptysis within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility as Measured by Number of Participants Who Complete the Neoadjuvant Gemcitabine/Nab-paclitaxel and HIGRT Regimen | approximately 6 months | The neoadjuvant regimen will be considered feasible if (a) the trial can accrue 25 patients in no more than 3 years and (b) if at least 17 of the 25 patients adhere to the neoadjuvant regimen and c) the acute grade 3+ non-hematologic acute toxicity is less than 50% (exclusing fatigue and alopecia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Grade >/=2 Acute Toxicity | 60 days post surgery | CTCAE version 4 will be used for all toxicity assessments. The acute toxicity rate, defined as any non-hematologic grade 2+ toxicity occurring during HIGRT treatment through 60 days post-treatment, will be estimated with its exact 80% confidence interval. Likewise, we will determine the rate of grade 2+ hematologic toxicity occurring during treatment through 60 days post treatment and the proportion of patients requiring treatment breaks longer than 5 days. |
| Number of Participants Who Underwent Surgical Resection | 14-30 days post surgery | Patients who undergo surgical resection will be documented |
| Number of Participants Who Received an R0 Resection | 14-30 days post surgery | Pathologic review will determine if an R0 resection has been performed. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy/Radiation/Surgery Gemcitabine/nab-Paclitaxel: Prospective, single arm study ; eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel. All chemotherapy administered to study subjects is standard of care. The chemotherapy combination, gemcitabine/nab-paclitaxel, is considered to be a standard-of-care, non-investigational chemotherapy combination; chemotherapy dosing and treatment schedule will be managed by the treating medical oncologist. Restaging will be completed post chemotherapy.
Radiation therapy: 5 fractions of hypofractionated IGRT or IMRT at 5Gy per fraction will be delivered before surgery. Restaging will be completed post radiation therap | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Chemotherapy/Radiation/Surgery |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 40 |
| other Total, other adverse events | 30 / 40 |
| serious Total, serious adverse events | 3 / 40 |
Outcome results
Primary
Feasibility as Measured by Number of Participants Who Complete the Neoadjuvant Gemcitabine/Nab-paclitaxel and HIGRT Regimen
The neoadjuvant regimen will be considered feasible if (a) the trial can accrue 25 patients in no more than 3 years and (b) if at least 17 of the 25 patients adhere to the neoadjuvant regimen and c) the acute grade 3+ non-hematologic acute toxicity is less than 50% (exclusing fatigue and alopecia).
Time frame: approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy/Radiation/Surgery | Feasibility as Measured by Number of Participants Who Complete the Neoadjuvant Gemcitabine/Nab-paclitaxel and HIGRT Regimen | 39 Participants |
Secondary
Number of Participants Experiencing Grade >/=2 Acute Toxicity
CTCAE version 4 will be used for all toxicity assessments. The acute toxicity rate, defined as any non-hematologic grade 2+ toxicity occurring during HIGRT treatment through 60 days post-treatment, will be estimated with its exact 80% confidence interval. Likewise, we will determine the rate of grade 2+ hematologic toxicity occurring during treatment through 60 days post treatment and the proportion of patients requiring treatment breaks longer than 5 days.
Time frame: 60 days post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy/Radiation/Surgery | Number of Participants Experiencing Grade >/=2 Acute Toxicity | 10 Participants |
Secondary
Number of Participants Who Received an R0 Resection
Pathologic review will determine if an R0 resection has been performed. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
Time frame: 14-30 days post surgery
Population: Participants who underwent surgical resection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy/Radiation/Surgery | Number of Participants Who Received an R0 Resection | 18 Participants |
Secondary
Number of Participants Who Underwent Surgical Resection
Patients who undergo surgical resection will be documented
Time frame: 14-30 days post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy/Radiation/Surgery | Number of Participants Who Underwent Surgical Resection | 24 Participants |