SMAD4 Tailored Neoadjuvant Therapy for the Treatment of Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma, SMART-PANC Trial

Summary

This phase II trial tests the impact of using SMAD4-mutant status to personalize chemotherapy in treating patients with pancreatic ductal adenocarcinoma (PDAC) that can be removed by surgery (resectable) or that may be between resectable and unresectable (borderline resectable) before undergoing surgery (neoadjuvant). PDAC is one of the most aggressive and fastest growing tumors. SMAD4, a tumor suppressor gene, acts like a brake on cell growth and helps to prevent tumor cells from growing. However, losing it makes the tumor more aggressive and often resistant to standard of care (SOC) treatments regimens, such as gemcitabine with nab-paclitaxel and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic (DNA) and may kill tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Fluorouracil, a type of antimetabolite, stops cells from making DNA and it may kill tumor cells. Leucovorin is a form of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Instead of a one-sized fits all treatment approach with SOC therapies, matching therapy based on SMAD4 mutation status may use this specific genetic weakness against the tumor. This approach to neoadjuvant therapy may dramatically alter the path of treatment and improve outcomes, including complete resection rates, in patients with resectable or borderline resectable PDAC.

Conditions

• Borderline Resectable Pancreatic Ductal Adenocarcinoma
• Resectable Pancreatic Ductal Adenocarcinoma

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo CT

OTHER

Electronic Health Record Review

Ancillary studies

DRUG

Fluorouracil

Given fluorouracil

DRUG

Gemcitabine

Given gemcitabine

DRUG

Irinotecan

Given irinotecan

DRUG

Leucovorin

Given leucovorin

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Nab-paclitaxel

Given nab-paclitaxel

DRUG

Oxaliplatin

Given oxaliplatin

RADIATION

Radiation Therapy

Undergo radiation therapy

PROCEDURE

Surgical Procedure

Undergo surgical resection

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Northwestern University

  lead OTHER

Principal Investigators

• Brett L Ecker, MD · Northwestern University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-02-03

Primary Completion

2030-02-03

Completion

2031-02-03

FDA Drug

Yes

Countries

• United States

Study Locations