A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors

Resveratrol has been shown to activate a protein called Notch-1. Signaling of Notch-1 has been shown to prevent tumor cell growth. Resveratrol has also been shown to prevent growth of tumors in mice. The purpose of this study is to examine the effects of resveratrol and Notch-1 on neuroendocrine tumor tissue and to examine how people with neuroendocrine tumors who take resveratrol for up to three months tolerate the product.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumor
• Intervention / Treatment: Dietary supplement: Resveratrol

Detailed Description

Patients will be treated with a dose of 5 gm/day of resveratrol orally, in two divided doses of 2.5 gm each without a break in therapy for a total of three cycles. All patients who receive at least one dose of resveratrol will be evaluated for toxicity and tolerability. Toxicities will be assessed every 28 days while the study drug is being taken by the patient. Pill bottles will be reviewed at this visit as well to ensure compliance with the study medication. Toxicities will be graded according to the NCI Common Toxicity Criteria. Blood will be drawn for a complete blood count and comprehensive metabolic panel. In addition, one vial of serum will be stored at the time of each toxicity assessment for later analysis of resveratrol levels. This level must be drawn one hour after the morning dose and the participants will be instructed to alter the time of the morning dose so as to allow proper timing with the scheduled blood draw.

During the third cycle of treatment, a post-treatment biopsy will be obtained for study related purposes and will be processed only for research related purposes.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ECOG performance status of 0-2
2. Age >18 years old
3. Women who are not postmenopausal must have a negative enrollment blood test and agree to use an effective mode of contraception while taking the study medication
4. Greater than four weeks must have elapsed since any previous therapy was administered for the neuroendocrine tumor, including surgery, radiation, chemotherapy or local liver therapy.
5. Octreotide use is allowed but must be initiated at least four weeks prior to enrollment and to the pre-treatment biopsy
6. Able to give informed consent and willing to undergo the post-treatment research biopsy
7. Must be able to take oral medications and be without GI tract obstructive symptoms
8. Subjects with another malignancy for which they are either undergoing treatment with chemotherapy or radiation, or with a malignancy for which such treatments have been recommended, would be excluded or withdrawn from the study.
9. Must agree to abstain from excessive alcohol, as defined by greater than the equivalent of three glasses of wine per day or one six pack of beer per day

Exclusion Criteria:

1. The principal investigator will review each subject's current medications prior to enrollment of the study to ensure that the administration of Resveratrol will not affect their current medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Resveratrol; 5 gm/day of resveratrol orally, in two divided doses of 2.5 gm each without a break in therapy for a total of three cycles.	Dietary supplement: Resveratrol; 5 gm/day of resveratrol orally, in two divided doses of 2.5 gm each without a break in therapy for a total of three cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels	1. The investigators aim primarily to show that resveratrol therapy in patients with low-grade GI neuroendocrine tumors will significantly increase Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels. Endpoints: The primary endpoint will be the level of expression of full length Notch1, cleaved Notch1, HES-1, and ASCL-1, as measured by Western blot using quantitative densitometry. The pre-treatment and post-treatment biopsies will be processed and analyzed simultaneously so as to minimize inter-test variability.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demonstrate that resveratrol at 5 gm per day will be well tolerated with minimal dose limiting toxicities in this patient population.	Frequency of grade three or greater toxicities as defined by the NCI Common Toxicity Criteria.	1 year
Describe the effect of resveratrol on tumor growth as demonstrated by standard cross sectional imaging and tumor markers.	The level of tumor markers (eg, chromogranin, 5-HIAA, gastrin, and others) pre-treatment will be compared to the post-treatment levels (collected every three months) as a measure of tumor response. In addition, serial axial imaging will be used to document tumor response rates according to standard Response Evaluation Criteria in Solid Tumors (RECIST).	1 year

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Emily R. Winslow, MD, University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 11, 2018

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (ESTIMATE): November 22, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: gastrointestinal neuroendocrine tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neuroendocrine Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: 2011-0097 (OTHER: Institutional Review Board); A539740 (OTHER: UW Madison); SMPH\SURGERY\GEN SURG (OTHER: UW Madison); OS10325 (OTHER: University of Wisconsin Carbone Cancer Center); NCI-2011-03685 (REGISTRY: NCI Trial ID)