SMART-PANC: SMAD4 Tailored Neoadjuvant Therapy for Pancreatic Cancer, A Phase ll Non-Randomized, Single Center Pilot Study
Northwestern University
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.
Description
PRIMARY OBJECTIVE: I. To determine the R0/R1 surgical resection rate among patients with SMAD4-mutant pancreatic cancer treated with gemcitabine/nab-paclitaxel (Cohort A). SECONDARY OBJECTIVES: I. To estimate the trial participation rate among patients approached for enrollment, defined as the proportion of patients who consent and enroll among those approached, with a target participation rate of ≥ 70%, and to monitor this rate continuously during accrual. II. To estimate the R0/R1 surgical resection rate among SMAD4 wild-type patients treated with physician choice chemotherapy (Cohort B)…