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

• ClinicalTrials.gov Identifier: NCT01476592
• Recruitment Status: Completed
• First Posted: November 22, 2011
• Last Update Posted: November 18, 2019
• Sponsor: University of Wisconsin, Madison
• Information provided by (Responsible Party): University of Wisconsin, Madison

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	Not Applicable

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 (Clinical Trial)
• 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: December 2011
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: October 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.

Outcome Measures

Primary Outcome Measures :

1. Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels [ Time Frame: 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 :

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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

University of Wisconsin, Madison

Investigators

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

More Information

Additional Information:

University of Wisconsin Carbone Cancer Center 

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01476592
• Other Study ID Numbers: 2011-0097; OS10325 ( Other Identifier: University of Wisconsin Carbone Cancer Center ); 2011-0097 ( Other Identifier: Institutional Review Board ); A539740 ( Other Identifier: UW Madison ); SMPH\SURGERY\GEN SURG ( Other Identifier: UW Madison ); NCI-2011-03685 ( Registry Identifier: NCI Trial ID )
• First Posted: November 22, 2011
• Last Update Posted: November 18, 2019
• Last Verified: November 2018

Keywords provided by University of Wisconsin, Madison:

gastrointestinal neuroendocrine tumor

Additional relevant MeSH terms:

Neuroendocrine Tumors; Digestive System Neoplasms; Gastrointestinal Neoplasms; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Resveratrol; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Enzyme Inhibitors; Platelet Aggregation Inhibitors