Chemoprevention With Tamoxifen in Pre-Invasive Pancreas Mucinous Cystic Neoplasms Not Undergoing Immediate Resection (MCN_Tam)

A Pilot Study of Chemoprevention With Tamoxifen in Patients With Pre-Invasive Pancreas Mucinous Cystic Neoplasms Who Will Not Undergo Immediate Resection

This is an open-label pilot study of tamoxifen as chemoprevention in patients with pancreatic MCN who will not undergo immediate resection. Up to 15 subjects will be enrolled and take tamoxifen 20mg by mouth daily for up to 24 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cyst; Pancreatic Mucinous Cystic Neoplasm
• Intervention / Treatment: Drug: Tamoxifen 20mg

Detailed Description

This is an open-label pilot study of tamoxifen as chemoprevention in patients with pancreatic MCN who will not undergo immediate resection. Up to 15 subjects will be enrolled and take tamoxifen 20mg by mouth daily for up to 24 weeks. The primary endpoints are feasibility of tamoxifen as chemoprevention in patients with pancreatic MCN and objective response rate as assessed by MRI. This study is intended to inform the design of a subsequent trial formally powered to detect the benefit of tamoxifen in treating pancreatic MCN.

The clinical features of pancreatic MCN support the influence of sex hormones in the pathogenesis of the disease. Anti-hormonal therapy may therefore constitute an effective approach to treatment of MCN and chemoprevention of pancreatic adenocarcinoma. Preliminary analyses from preclinical studies suggest that tamoxifen inhibits proliferation and apoptosis in MCN epithelial cells and fibroblasts. We hypothesize that in humans, treatment with tamoxifen will lead to cyst regression or stabilization and may spare or delay the need for resection.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Peggy Heires, BA; Phone Number: 402-559-7078; Email: peggy.heires@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center
      • Principal Investigator: Kelsey Klute, MD
      • Contact: Christina Hoy, DNP; Email: choy@nebraskamed.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 19 years
2. Clinically diagnosed pre-invasive pancreatic MCN
3. Mucinous cystic neoplasm is measurable by cross-sectional imaging
4. Surgical resection of the lesion is not planned due to cyst features, patient factors or patient preference
5. Females of reproductive potential and males with partners of reproductive potential must agree to employ two methods contraception throughout the study and for up to 3 months following treatment. Non-child-bearing potential is defined as age 45 years or older and no menses for greater than or equal to 12 months or any age with surgical removal of the uterus and/or both ovaries. See section 3.3 for more details
6. Estimated glomerular filtration rate (eGFR) > 30mL/min/1.73m2
7. Willing and able to provide informed consent to and abide by the protocol

Exclusion Criteria:

1. Presence of invasive pancreatic adenocarcinoma or high-grade dysplasia
2. Presence of a solid component or mural nodule, main pancreatic duct dilation or abrupt caliber change, obstructive jaundice, lymphadenopathy
3. Current or prior use of tamoxifen or another estrogen antagonist including but not limited to clomifene, raloxifene, fulvestrant, anastrazole; subjects who have previously used an estrogen antagonist are eligible provided the last use was at least 5 years prior to enrollment.
4. Current or planned use of hormonal treatments including estrogen, progesterone, androgens, hormone replacement therapy or other types of hormonal contraceptives including implants and depot injections; levonorgestrel-releasing intrauterine device (IUD) is permitted.

5. Contraindications to tamoxifen including:

   1. Pregnancy or nursing
   2. Known allergy or hypersensitivity to tamoxifen
   3. Cataracts which affect visual acuity (ie. symptomatic)
   4. Retinopathy which affects visual acuity (ie. symptomatic)
   5. Current warfarin use
   6. History of deep vein thrombosis or pulmonary embolism or other condition which, in the discretion of the treating physician, may significantly increase the individual's risk of venous thromboembolism
   7. History of stroke
   8. Known endometrial hyperplasia or personal history of endometrial carcinoma, uterine sarcoma and uterine carcinosarcoma
6. History of intestinal disease or major gastric surgery likely to alter absorption of tamoxifen or inability to swallow oral medications
7. Uncontrolled illness including but not limited to ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina or uncontrolled cardiac arrhythmias, or other conditions which might jeopardize or preclude the ability of the patient to take tamoxifen or the safety of follow-up visits, scans and procedures
8. Elective surgery planned for the study period
9. Participation in another clinical study with an investigational product during the last 28 days
10. Any subject, in the opinion of the treating physician, who will not be able to tolerate treatment, or the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifen; Tamoxifen 20mg by mouth daily for up to 6 months	Drug: Tamoxifen 20mg; Tamoxifen is a nonsteroidal antiestrogen for oral administration.; Other Names: Soltamox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility, by adherence rate	Adherence rate, defined as the proportion of subjects who take ≥70% of the prescribed tamoxifen doses with adherence at least 60%, meaning ≥60% of subjects take ≥70% of the prescribed tamoxifen doses	6 months (approximately 180 days)
Feasibility, by retention rate	Retention rate, defined as the proportion of subjects who complete imaging and study procedures at the 6-month visit with retention of at least 50%, meaning at least 50% of subjects complete imaging and study procedures at the 6-month visit	6 months (approximately 180 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) of pancreatic MCN	The ORR will be estimated based on the proportion of subjects with complete or partial response on MRI/MRCP; partial response is defined by ≥ 20% decrease in maximal cyst diameter.	12 months (approximately 360 days)

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Kelsey Klute, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Cysts; Pancreatic Diseases; Neoplasms; Pancreatic Cyst; Neoplasms, Cystic, Mucinous, and Serous; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: 0074-24-CB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No