This phase II trial tests how well gemcitabine, cisplatin and nab-paclitaxel given before surgery (neoadjuvant) works in treating patients with pancreatic cancer that can be removed by surgery (resectable) or that is borderline resectable. The standard treatment for resectable and borderline resectable pancreatic cancer is a combination of surgery and chemotherapy. Neoadjuvant therapy has been shown to improve overall survival compared to patients receiving surgery first. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel, an antimicrotubule agent that stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel may have fewer side effects and work better than other forms of paclitaxel. Gemcitabine, cisplatin and nab-paclitaxel may be an effective neoadjuvant treatment option for patients with resectable or borderline resectable pancreatic cancer.
PRIMARY OBJECTIVE: I. Determine the major pathological response rate, feasibility and safety of biweekly gemcitabine, cisplatin and nab-paclitaxel (GCN) in the neoadjuvant setting for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma. SECONDARY OBJECTIVE: I. Determine if neoadjuvant GCN increases tumoral infiltration of lymphocytes with local and systemic phenotypic features that assist in the antitumor immune response. OUTLINE: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 15 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease, partial or complete response undergo surgical resection per standard of care. Additionally, patients undergo biopsy on study and undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) at pre-study and on study. After completion of study treatment, patients are followed up every 3-4 months for up to 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Undergo biopsy
Undergo blood sample collection
Given IV
Undergo CT
Given IV
Undergo MRI
Given IV
Undergo surgical resection
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGClinical Response Rate to Neoadjuvant Chemotherapy
Clinical response is defined as biochemical, radiological, pathological response or stable disease. • Biochemical response (or CA 19-9 response) is defined as \>50% decrease from baseline with tumor response. Radiologic response is defined as complete response (CR), partial response (PR) or stable disease (SD) after the neoadjuvant therapy per RECIST 1.1. Pathologic response is defined by CAP scoring system as 0 (complete response), 1 (moderate response), 2 (minimal response) and 3 (poor or no response). Stable disease is defined as the absence of biochemical response (\>50% CA 19-9 reduction), radiological response (per RECIST 1.1), or major pathological response (CAP Score 0-1), without metastasis / unresectability, and patient undergoes surgical resection. Clinical response rate (including clinical, biochemical, radiological, pathological response or stable disease) will be reported as a proportion, with an exact 90% confidence interval estimated using the Clopper-Pearson method.
Time frame: Up to 24 months
Treatment Completion
Feasibility will be defined as completion of all preoperative and operative therapy. Treatment completion will reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.
Time frame: Up to 24 months
Incidence of Adverse Events (AEs)
AEs, with severity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be reported, using frequencies and percentages for each toxicity.
Time frame: Up to 28 days after last dose of study treatment
Radiologic Response Rate
Radiological response rate will be defined as complete response, partial response or stable disease after study treatment evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. Radiologic response rate will be reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.
Time frame: Up to 24 months
Pathological Response Rate
To assess the major pathological response rate (CAP 0-1) in the surgical resection specimen
Time frame: Up to 24 months
Neoadjuvant Systemic Chemotherapy Rate
To assess the rate of neoadjuvant systemic chemotherapy completion (Duration 4 months) without dose reduction
Time frame: Up to 4 months
R0 Resection Rate
R0 resection indicates a microscopically margin-negative resection. R0 resection rate will reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.
Time frame: At time of surgery
Nodal Status
N0, N1, and N2 will be reported using frequencies and percentages.
Time frame: Up to 24 months
Recurrence-Free Survival (RFS)
RFS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median RFS will be estimated using the Brookmeyer-Crowley approach.
Time frame: From surgery to recurrence or death, assessed up to 24 months
Overall Survival (OS) Rate
OS will be estimated using the Kaplan-Meier method, and median survival will be calculated. A 95% confidence interval will be estimated using the Brookmeyer-Crowley approach.
Time frame: From study treatment start to date of death, assessed up to 24 months
Carbohydrate Antigen (CA)19-9 response
CA19-9 response will be defined as \> 50% decrease from baseline will be correlated with tumor response. CA19-9 will be reported as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method. CA19-9 will be correlated with RFS and OS using log-rank tests and Cox proportional hazards regression. Model assumptions will be checked and verified.
Time frame: Up to 24 months
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