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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01476592
First received: November 9, 2011
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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 Intervention
Neuroendocrine Tumor
Dietary Supplement: Resveratrol

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 7
Study Start Date: December 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01476592

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

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01476592     History of Changes
Other Study ID Numbers: 2011-0097
Study First Received: November 9, 2011
Last Updated: August 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
gastrointestinal neuroendocrine tumor

Additional relevant MeSH terms:
Resveratrol
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms
Neuroendocrine Tumors
Digestive System Diseases
Gastrointestinal Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticarcinogenic Agents
Antimutagenic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antioxidants
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014