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

Sponsor

University of Wisconsin, Madison (Other)

Overall Status

Completed

CT.gov ID

NCT01476592

Collaborator

(none)

Enrollment

Location

Arm

82.3

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumor	Dietary Supplement: Resveratrol	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 11, 2018

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels [1 year]
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.

Secondary Outcome Measures

Demonstrate that resveratrol at 5 gm per day will be well tolerated with minimal dose limiting toxicities in this patient population. [1 year]
Frequency of grade three or greater toxicities as defined by the NCI Common Toxicity Criteria.
Describe the effect of resveratrol on tumor growth as demonstrated by standard cross sectional imaging and tumor markers. [1 year]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ECOG performance status of 0-2
Age >18 years old
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
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.
Octreotide use is allowed but must be initiated at least four weeks prior to enrollment and to the pre-treatment biopsy
Able to give informed consent and willing to undergo the post-treatment research biopsy
Must be able to take oral medications and be without GI tract obstructive symptoms
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.
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:

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.