Neoadjuvant Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

Phase 2RecruitingNCT05825066

Wake Forest University Health Sciences64 enrolled

Overview

The objective of this research is to find out what effects (good and bad), the sequence of Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX, the standard chemotherapy for pancreatic cancer, has on participants and their condition. Gemcitabine - Abraxane (nab-Paclitaxel) and mFOLFIRINOX has been approved by the US Food and Drug Administration (FDA) as first line treatment for advanced pancreatic cancer. The sequence of Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX has not been approved by the FDA for treatment of pancreatic cancer.

Primary Objective: \- The primary objective of this study is to evaluate the efficacy of sequential Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in improving R0 resection rate in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer. Secondary Objectives: * Evaluate the safety and tolerability of sequential Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer * Evaluate progression-free survival (PFS) in patients treated with sequential Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines * Evaluate overall survival (OS) in patients treated with sequential Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer * Evaluate the objective response rate (ORR) in patients treated with sequential Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer. * Evaluate the disease control rate (DCR) in patients treated with Gemcitabine - Abraxane (nab-Paclitaxel) followed by mFOLFIRINOX in patients with borderline resectable pancreatic cancer and locally advanced unresectable pancreatic cancer.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Interventions

Nab paclitaxelDRUG

The intervention will be administered on an outpatient basis. The patients on this study will begin treatment with GA for one month and then transition to mFFX for one month. The patient will come off of the sequence study intervention if the imaging after the 2nd month shows unequivocal progression. After four months of sequential neoadjuvant therapy the patient will come off study and can proceed to surgery, radiation, or extended course of chemotherapy as determined by the multidisciplinary tumor board consensus or the treating physician.

GemcitabineDRUG

Radiological AssessmentsOTHER

CT imaging of chest abdomen and pelvis will be performed every 8 weeks. MRI may be used.

mFOLFIRINOXDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients must have histologically or cytologically proven adenocarcinoma of the pancreas. Patients with mixed tumor with predominant adenocarcinoma pathology can be enrolled * Patients with borderline resectable or locally advanced pancreatic adenocarcinoma as assessed per NCCN guidelines (either pancreatic head, neck, uncinate process, or body/tail) or institutional multidisciplinary consensus * Age 18 or above * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 * Patients must have organ and marrow function as defined below: Hemoglobin\* ≥8 g/dL Absolute neutrophil count ≥1,500/mcL Platelets\* ≥100,000/mcL Total bilirubin\* ≤1.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal Creatinine ≤1.5 X institutional upper limit of normal or CrCL\>50 * It is acceptable to transfuse packed red blood cells (PRBC) and platelets at the time of enrollment to meet the eligibility criteria. * If obstructive jaundice is present, consider ursodiol or a biliary drainage procedure. If the total bilirubin can be reduced or kept to less than or equal to 3 mg/dL, then this inclusion criteria is met. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). * Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative) Exclusion Criteria: * Patients who have had prior chemotherapy with gemcitabine and/or nab-paclitaxel or FOLFIRINOX for pancreatic cancer * Patients receiving any other investigational anti-neoplastic agents * History of malignancy in last 3 years except cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer, who are considered to be eligible * Patients with active and uncontrolled bacterial, viral or fungal infection requiring systemic therapy. Patients can be reevaluated for the study if the infection is deemed to be under control and the systemic therapy for the infection is completed * Uncontrolled intercurrent illness including, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the patient's safety * Patients with known diagnosis of interstitial lung disease, sarcoidosis, pulmonary fibrosis, or pneumonitis requiring oxygen supplementation. Those that do not require oxygen supplementation are eligible. * Patients who have undergone surgery, other than diagnostic or minor procedures, within 4 weeks prior to the initiation of study treatment * Patients who are pregnant or breastfeeding

Outcomes

Primary Outcomes

R0 Resection Rate - Borderline Resectable Prostate Cancer Participants

The R0 resection is assessed only in patients who undergo surgery. R0 resection is a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. Participants are considered to be evaluable if they receive at least one sequence of treatments with GA and mFFX (1 cycle GA followed by 1 cycle of m FFX). Primary analysis for each cohort will calculate the R0 resection rate with one-sided 95% confidence interval.

Time frame: 9 months

R0 Resection Rate - Locally Advanced Prostate Cancer Participants

Time frame: 9 months

Secondary Outcomes

Incidences of Adverse Events

The incidence of treatment-emergent toxicities/adverse events (AEs) and Serious Adverse Events (SAEs) in terms categorized and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5). Incidence tables will be generated to summarize incidence of patients reporting at least one episode of each specific adverse event, incidence of adverse events causing withdrawals and incidence of serious adverse events, separated by cohort.