PROACTIVE: Surgical Resection Outcomes in Locally Advanced and Unresectable Pancreatic Cancer After Neoadjuvant Chemotherapy

Brief summary public domain (ClinicalTrials.gov)

This clinical trial tests how well surgical resection after chemotherapy given before surgery to make the tumor smaller (neoadjuvant) works to treat pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) and that cannot be removed by surgery (unresectable). In general, surgery is considered the most effective treatment for pancreatic cancer, especially when the cancer is localized and has not spread to other organs. However, most patients with pancreatic cancer are not candidates for surgical removal because the cancer has grown into or close to nearby arteries, veins, or organs and there is a concern of damaging these nearby structures. Researchers want to find out if surgery after neoadjuvant chemotherapy can be done safely to completely remove the tumor in patients with locally advanced and unresectable pancreatic cancer.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. Evaluate the R0 resection in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. II. To measure disease free survival (DFS) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. III. To evaluate the correlation between post-neoadjuvant/preoperative radiological staging and pathologic staging. IV. To estimate time to distant metastases (TDM) in patients in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. EXPLORATORY OBJECTIVES: I. To evaluate the correlation between post-neoadjuvant/preoperative radiological staging and pathologic staging. II. To evaluate objective response rate (ORR) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy. III. To assess if mutations on next-generation sequencing (NGS) testing and the change in circulating tumor deoxyribonucleic acid (ctDNA) pre- and post-operative is predictive of DFS or OS in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. IV. To evaluate the rate of unresectability in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy. V. To evaluate pathologic tumor response and rate of pathologic complete response (pCR) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. VI. To evaluate correlation between R0 resection rate and pathologic treatment response and survival outcomes. VII. To evaluate number of cycles of perioperative chemotherapy received in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. VIII. To evaluate the adverse event profile in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. IX. To evaluate the physical functioning, nausea/vomiting, and diarrhea, as measured with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. X. To evaluate the average operative time in minutes in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. XI. To evaluate the estimated blood loss (mL) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. XII. To assess the length of hospital, stay in for patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. XIII. To evaluate the incidence of thrombosis in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery. OUTLINE: Patients undergo laparoscopy followed by surgical resection with pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy at the discretion of the surgeon within 2-8 weeks following completion of standard of care neoadjuvant chemotherapy regimen. Patients undergo computed tomography (CT) and blood sample collection throughout the study and/or magnetic resonance imaging (MRI) during screening. Patients also undergo tissue collection at time of surgical resection on study. After completion of study intervention, patients are followed up at 30 days, every 3 months for the first year, then every 6 months until 2 years.

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo blood and tissue sample collection

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo CT

Intervention public domain (ClinicalTrials.gov)

Procedure: Distal Pancreatectomy. Undergo distal pancreatectomy

Intervention public domain (ClinicalTrials.gov)

Procedure: Laparoscopy. Undergo laparoscopy

Intervention public domain (ClinicalTrials.gov)

Procedure: Magnetic Resonance Imaging. Undergo MRI

Intervention public domain (ClinicalTrials.gov)

Procedure: Pancreaticoduodenectomy. Undergo pancreaticoduodenectomy

Intervention public domain (ClinicalTrials.gov)

Other: Questionnaire Administration. Ancillary studies

Intervention public domain (ClinicalTrials.gov)

Procedure: Surgical Procedure. Undergo surgical resection

Arm public domain (ClinicalTrials.gov)

Treatment (surgical resection) (experimental): Patients undergo laparoscopy followed by surgical resection with pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy at the discretion of the surgeon within 2-8 weeks following completion of standard of care neoadjuvant chemotherapy regimen. Patients undergo CT and blood sample collection throughout the study and/or MRI during screening. Patients also undergo tissue collection at time of surgical resection on study.

Primary outcome public domain (ClinicalTrials.gov)

R0 resection rate. Will be defined as the proportion of patients with negative resection margins after undergoing surgery. Time frame: At time of surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival. Time frame: Up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Disease-free survival. Time frame: Up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Time to locoregional recurrence. Time frame: Up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Time to distant metastases. Time frame: Up to 2 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Histologic or cytologic proof of pancreatic adenocarcinoma * Locally advanced, stage III (T4NxM0) and unresectable by National Comprehensive Cancer Network (NCCN) Guidelines prior to perioperative chemotherapy * Patients must have measurable disease at diagnosis per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 * At least 4 cycles of perioperative chemotherapy (gemcitabine \[Gem\]/nab-paclitaxel or fluorouracil, irinotecan, leucovorin and oxaliplatin \[FOLFIRINOX\]) received with no evidence of progression on restaging scans per RECIST 1.1 * Age ≥ 18 years * Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcl * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) if no biliary stenting has been done or 2.0 x ULN if patient is status post (s/p) biliary stenting or two down trending values * Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SPGT\]) ≤ 2.5 X ULN * Creatinine (Cr) ≤ 1.5 mg/dL or Cr clearance ≥ 30 mL/min (as estimated by Cockcroft Gault) * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Patient with known distant metastases * Patients who have not recovered from adverse events of chemotherapy due to agents administered more than 4 weeks earlier * Patients who have progressed on 2 prior systemic chemotherapy lines or received prior radiotherapy for pancreatic cancer * Patients may not be receiving any other investigational agents * Uncontrolled intercurrent illness including, but not …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 2 participants (estimated).