PROACTIVE: Surgical Resection Outcomes In Locally Advanced And Unresectable Pancreatic Cancer After Neoadjuvant Chemotherapy

Study Overview

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

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.

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.

Locally Advanced Pancreatic Adenocarcinoma
Stage III Pancreatic Cancer American Joint Committee on Cancer v8
Unresectable Pancreatic Adenocarcinoma

PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
PROCEDURE: Distal Pancreatectomy
PROCEDURE: Laparoscopy
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Pancreaticoduodenectomy
OTHER: Questionnaire Administration
PROCEDURE: Surgical Procedure
PROCEDURE: Total Pancreatectomy

3P-23-5
NCI-2023-09210 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
3P-23-5 (OTHER Identifier) (OTHER: USC / Norris Comprehensive Cancer Center)
P30CA014089 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-11-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-10-17
First Submitted that Met QC Criteria 2023-11-09	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-10-21
First Posted (ACTUAL) 2023-11-15	Results First Posted N/A	Last Verified 2024-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (surgical resection) 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 re	PROCEDURE: Biospecimen Collection Undergo blood and tissue sample collection PROCEDURE: Computed Tomography Undergo CT PROCEDURE: Distal Pancreatectomy Undergo distal pancreatectomy PROCEDURE: Laparoscopy Undergo laparoscopy PROCEDURE: Magnetic Resonance Imaging Undergo MRI PROCEDURE: Pancreaticoduodenectomy Undergo pancreaticoduodenectomy OTHER: Questionnaire Administration Ancillary studies PROCEDURE: Surgical Procedure Undergo surgical resection PROCEDURE: Total Pancreatectomy Undergo total pancreatectomy

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (surgical resection)

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 re

PROCEDURE: Biospecimen Collection

Undergo blood and tissue sample collection

PROCEDURE: Computed Tomography

Undergo CT

PROCEDURE: Distal Pancreatectomy

Undergo distal pancreatectomy

PROCEDURE: Laparoscopy

Undergo laparoscopy

PROCEDURE: Magnetic Resonance Imaging

Undergo MRI

PROCEDURE: Pancreaticoduodenectomy

Undergo pancreaticoduodenectomy

OTHER: Questionnaire Administration

Ancillary studies

PROCEDURE: Surgical Procedure

Undergo surgical resection

PROCEDURE: Total Pancreatectomy

Undergo total pancreatectomy

Primary Outcome Measures	Measure Description	Time Frame
R0 resection rate	Will be defined as the proportion of patients with negative resection margins after undergoing surgery.	At time of surgery

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival	Determined from the date of registration to the date of death due to any cause.	Up to 2 years
Disease-free survival	Determined from the date of registration to the date of progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to any cause, whichever occurs first.	Up to 2 years
Time to locoregional recurrence	Determined from the date of registration to the date of locoregional recurrence after resection.	Up to 2 years
Time to distant metastases	Determined from the date of registration to the date of metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection.	Up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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 limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Steven R Grossman, MD, University of Southern California

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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