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 is more feasible and could improve outcomes 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.
Histologically or cytologically confirmed - resectable and borderline resectable pancreatic ductal adenocarcinoma
Resectability will be defined as per National Comprehensive Cancer Network (NCCN) guidelines using cross-sectional imaging (contrast-enhanced computed tomography or magnetic resonance imaging scans of the abdomen, and pelvis)
Decisions about resectability status will be made in consensus at multidisciplinary meetings/discussions
No interface of the tumor with celiac artery, common hepatic artery (CHA), or superior mesenteric arteries (SMA) (and, if present, variants)
Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)"
Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations
Pregnancy (positive pregnancy test) or lactation
Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (radiosurgery [RS]; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
Single group
Biopsy
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cisplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Gemcitabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Nab-paclitaxel
DrugGiven IV
Pancreatic Surgical Procedure
Procedure/SurgeryUndergo surgical resection
Clinical 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.
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.
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.
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.
Pathological Response Rate
To assess the major pathological response rate (CAP 0-1) in the surgical resection specimen
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Georgetown University
Lead sponsor
Emory University
Collaborator
