Neoadjuvant Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

NCT ID: NCT05825066

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2029-07-31

Brief Summary

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.

Detailed Description

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.

Conditions

Pancreas Adenocarcinoma; Borderline Resectable Pancreatic Adenocarcinoma; Locally Advanced Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Chemotherapy (Gemcitabine and nab-Paclitaxel and mFOLFIRNIOX)

• Gemcitabine (1000 mg/m2 weekly, on day 1,8 and 15 OR 1000 mg/m2 weekly, on day 1 and 15 over 30 minutes after nab-paclitaxel infusion.
• nab-Paclitaxel (125 mg/m2 weekly, on days 1,8, and 15 OR on days 1 and 15 as a 30-40 minute infusion administered first) for one month and then transition to mFOLFIRNIOX for one month

1 Cycle = 4 weeks: Day 1,8,15 in a 28 day cycle; 3 consecutive weeks (weeks 1, 2, and 3) of chemotherapy with 1 week off, OR

1 Cycle = 4 weeks: Day 1, 15 in a 28 day cycle; Every other week (weeks 1 and 3) of chemotherapy with 2nd and 4th week off

• mFOLFIRINOX: Oxaliplatin, 85 mg/m² IV once every two weeks over 2 hours on Day 1 Irinotecan, 150 mg/m² IV once every two weeks over 90 minutes on Day 1 5-FU, 2,400 mg/m² IV once every two weeks over 46-48 hours administered via infusion Leucovorin, 400 mg/m2 IV every two weeks over 90 minutes on Day 1

1. Cycle = 4 weeks, administration on Day 1 and Day 15 of each mFOLIRINOX cycle

Group Type: EXPERIMENTAL

Nab paclitaxel

Intervention Type: DRUG

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.

Gemcitabine

Intervention Type: DRUG

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.

Radiological Assessments

Intervention Type: OTHER

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

mFOLFIRINOX

Intervention Type: DRUG

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.

Interventions

Nab paclitaxel

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.

Intervention Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Radiological Assessments

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

Intervention Type: OTHER

mFOLFIRINOX

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.

Intervention Type: DRUG

Eligibility Criteria

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, then biliary drainage must be initiated and total bilirubin less than or equal to 3.0.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi K Paluri, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Wake Forest Baptist Comprehensive Cancer Center

Locations

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Study Coordinator

Role: CONTACT

ahumbert@wakehealth.edu

336-713-6912

Facility Contacts

Study Coordinator

Role: primary

ahumbert@wakehealth.edu

336-713-6912

Other Identifiers

WFBCCC 57222

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00095699

Identifier Type: -

Identifier Source: org_study_id