# Novel Therapy to Inhibit IPMN Progression

> **NIH NIH R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2022 · $686,204

## Abstract

ABSTRACT
Pancreatic ductal adenocarcinoma (PDA) is an incalcitrant malignancy with a 5-year survival of only 10%.
Therefore, targeting PDA precursors is an area of the highest priority. Amongst the most prevalent and easily
identifiable high-risk individuals with PDA precursors are patients with intraductal papillary mucinous neoplasm
(IPMN). Currently, patients with IPMN are managed with active surveillance (AS) and surgery to develop high-
risk stigmata. FDA-approved non-operative treatment of IPMN to prevent progression to PDA does not exist.
Challenges to developing an effective IPMN agent include identifying agents that can be tested in human
clinical trials, availability of an appropriate group of high-risk patients that can be entered into a clinical
prevention trial, and identifying potential biomarkers that could predict the efficacy of chemoprevention agents.
Recent work from our team has identified δ-tocotrienol (DT3) as a novel apoptosis-inducing agent for IPMN,
MUC4 as a driver as well as a predictive biomarker of IPMN progression, and an ideal cohort of motivated
patients with IPMN on AS, that provides new opportunities to address each of these high-priority challenges. In
a recently completed NCI-sponsored Phase I window-of-opportunity trial, we observed that DT3 is safe and
significantly induces apoptosis in the neoplastic cells of patients with IPMN. Our preliminary studies also
suggest that MUC4 expression is associated with response to DT3. Further, we observed that MUC4
expression in the background of oncogenic KRAS results in the development of IPMN in mouse pancreas.
Thus, the overall hypothesis for this proposal is that DT3 will block IPMN progression by targeting
pathways that are crucial for the initiation, maintenance, and progression of IPMN precursor lesions.
This hypothesis will be tested in two aims: In Aim 1, we will conduct a Phase II multi-institutional, randomized,
placebo-controlled trial of DT3 in the prevention of IPMN progression (106 patients/arm) utilizing individuals
from Moffitt Cancer Center, University of Nebraska Medical Center, and Mayo Clinic. The primary endpoint will
be IPMN Progression-Free Survival based on international guidelines criteria after three years. Patients will be
monitored with MRI/MRCP and endoscopic ultrasound-based on a standard of care. Further, correlative
studies will utilize radiomics and tissue and serum samples to study the biomarkers of response and discern
the mechanism of action of DT3. In Aim 2, we will define the molecular targets of DT3, the mechanism of
biochemical responses, and identify biomarkers of DT3 in the genetically engineered model of IPMN (KC-
MUC4 Tg) that harbors the mutational combination of oncogenic KRAS and inducible MUC4 overexpression.
Insights gained from the studies in Aim 2 will be validated with biospecimens obtained from patients in Aim 1.
This multidisciplinary proposal will allow opportunities to reduce PDA mortality by advancing a
promising ...

## Key facts

- **NIH application ID:** 10446455
- **Project number:** 1R01CA263575-01A1
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Surinder K. Batra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $686,204
- **Award type:** 1
- **Project period:** 2022-06-08 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446455

## Citation

> US National Institutes of Health, RePORTER application 10446455, Novel Therapy to Inhibit IPMN Progression (1R01CA263575-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10446455. Licensed CC0.

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