Study of IPMN Progression Prevention With Tocotrienol (SIPP-T3)

NCT06519097 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-21791R01CA263575
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, double-blind, placebo-controlled trial, investigating whether treatment with δ-tocotrienol (a.k.a. Delta-tocotrienol, abbreviated as DT3) will prevent the progression of Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas.

Conditions

Neoplasm of Pancreas; IPMN, Pancreatic

Keywords

Papillary Mucinous Neoplasm

Outcome Measures

Primary Outcomes (1)

• IPMN Progression Free Survival (iPFS)

  IPMN progression free survival (iPFS) defined as duration from date of randomization to date of event (IPMN progression), pursuant to the international Kyoto guidelines and the European guidelines. IPMN will be considered as having progressed if any one or more of the following features occur: (i) increase in size of \> 1 mm; (ii) development of any worrisome feature (growth rate ≥ 5 mm/ 2 years, main pancreatic duct dilatation from 5-9 mm, acute pancreatitis caused by IPMN, enhancing mural nodule \< 5 mm, increased serum CA 19-9 ≥ 37 U/ml, and cyst diameter ≥ 3 cm); or development of any high-risk stigmata (positive cytology for malignancy, solid mass, tumor related jaundice, enhancing mural nodule ≥ 5 mm, and main pancreatic duct dilatation ≥ 10 mm).

  Up to 60 Months

Secondary Outcomes (4)

• Time to Surgical Intervention (TSI)

  Up to 36 Months

• Bioavailability and Biodistribution

  Baseline, Month 6, 12, 24 and 36

• Acceptability of DT3 Treatment

  Baseline, Month 6, 12, 24 and 36

• Adherence of DT3 Treatment

  Baseline, Month 6, 12, 24 and 36

Study Arms (2)

Vitamin E Delta-tocotrienol (DT3)

EXPERIMENTAL

Patients will be given DT3 orally (by mouth) twice daily for 3 years

Drug: Vitamin E Delta Tocotrienol

Placebo

ACTIVE COMPARATOR

Patients will be given a placebo (a substance that looks like the study drug, but contains not active ingredients) orally (by mouth) twice daily for 3 years

Other: Placebo

Interventions

Vitamin E Delta Tocotrienol DRUG

Tocotrienols are natural vitamin E compounds that are known to have a neuroprotective effect at nanomolar concentration and anti-carcinogenic effect at micromolar concentration. 400 mg orally, twice daily

Also known as: DT3

Vitamin E Delta-tocotrienol (DT3)

Placebo OTHER

Placebo contains no active ingredients. 465 mg pure olive oil orally, twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, age ≥18 years.
• Evidence of IPMN as confirmed by MRI/Magnetic Resonance Cholangiopancreatography (MRCP) or pathology with biomarker results from Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS/FNA).
• IPMN must be suitable for active surveillance as defined by the international Kyoto guidelines and the European guidelines. Patients eligible for our study will have IPMN with no "high-risk stigmata" and no "worrisome features" and also have a neoplasm size of 1-\<3 cm.
• Able to complete all of the periodic activities of active surveillance as defined by the international Kyoto guidelines (2024) (Appendix VII) and the European guidelines (clinic visit evaluation, blood work, MRI/MRCP, and EUS).
• Eastern Cooperative Oncology Group = 0-2.
• Participants must have adequate organ and marrow function.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should undergo a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification (see Appendix VI). To be eligible for this trial, participants should be class I-II.
• Agrees to avoid dietary sources of increased DT3 and abstain from consuming non-study DT3 supplements, any other dietary supplements, herbal remedies and over the counter (OTC) medicines (except use of aspirin for which data will be collected in Oncore) beginning 3 days prior to start of study drug and throughout duration of the study. DT3 levels are extremely low in normal foods. Therefore, no specific foods need to be avoided. All supportive care medications, e.g., antiemetics, antidiarrheals growth factors etc. may be used at the discretion of the treating physician and according to institutional guidelines.
• Ability to understand and the willingness to sign a written informed consent document.
• Participants must agree to refrain from getting pregnant, breastfeeding or fathering a child for the duration of the study. Female participants of child-bearing potential and male participants with a female partner of child-bearing potential must agree to use an effective birth control method, as specified in the informed consent form, throughout the study and for 6 months following the last dose of DT3. For purposes of this study, child-bearing potential is defined as a premenopausal woman without permanent sterilization who has the potential to become pregnant by being exposed to sexual intercourse with a non-sterilized male partner. Examples of birth control methods include:
• Oral birth control pills
• Birth control patch
• Implanted (injectable contraceptive hormones or mechanical products such as intrauterine device)
• Barrier methods (such as: diaphragm, condoms, or spermicides)
• Tubal ligation or vasectomy

You may not qualify if:

• Evidence of Pancreatic Ductal Adenocarcinoma (PDAO or other cancers (excluding non-melanoma skin cancer) or metastatic disease.
• Concurrent systemic chemotherapy for any other cancer.
• Use of increased dietary sources of DT3, non-study DT3 supplements, any other dietary supplements, herbal remedies and OTC medicines (except use of aspirin for which data will be collected in Oncore) which may affect the study outcome unless the participant is willing to discontinue taking them 3 days prior to start of study drug DT3 and for the duration of the study. DT3 levels are extremely low in normal foods. Therefore, no specific foods need to be avoided.
• Participants may not be receiving any other investigational agents.
• History of allergic reaction attributed to vitamins.
• Patient is lactating, pregnant or planning to become pregnant during the trial.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• American River Nutrition, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6880, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Pancreatic Neoplasms; Pancreatic Intraductal Neoplasms

Interventions

tocotrienol, delta

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Mokenge P Malafa, MD, FACS

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: All eligible patients will be allocated randomly to one of 2 groups, the DT3 group and the Placebo group. Surgeons, medical oncologists, advanced practice professionals (APPs) (nurse practitioners and physician assistants) at the follow-up outpatient clinics, and patients will be blinded to the allocation. Patients in the DT3 group shall receive oral DT3 400 mg twice per day, and those in the placebo group shall receive oral placebo twice per day.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 25, 2024
• Study Start: July 9, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (2)