Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Neuroendocrine Tumors

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Gastrointestinal Diseases

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Neuroepithelioma

Platelet Aggregation Inhibitors

All Drugs and Chemicals

Resveratrol

Antioxidants

Protective Agents

Enzyme Inhibitors

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.

Emily R. Winslow, MD

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.

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.

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

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.

Frequency of grade three or greater toxicities as defined by the NCI Common Toxicity Criteria.

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).

University of Wisconsin, Madison

Adenocarcinoma

Rectal Neoplasms

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

STAGE I: Patients undergo an colorectal endoscopy. Patients whose biopsies confirm colorectal adenocarcinoma histology and require surgical resection continue on study stage 2.

STAGE II: Patients receive oral resveratrol on days 1-8. Patients undergo colorectomy on day 9. A tumor biopsy is performed during endoscopy and colorectomy for research purposes.

resveratrol

pharmacological study

laboratory biomarker analysis

Dean Brenner

This phase I trial is studying the side effects and best dose of resveratrol in treating patients with colorectal cancer that can be removed by surgery. Resveratrol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

OBJECTIVES:

I. Determine the relationship between oral dose of resveratrol and the colon mucosal levels of resveratrol and its metabolites in patients with resectable colorectal cancer.

II. Determine the relationship between colon mucosal levels of resveratrol and its metabolites and plasma concentrations of resveratrol and its metabolites in these patients.

III. Determine cyclooxygenase-2 (COX-2) expression in colorectal cancer tissue before and after treatment in these patients.

IV. Determine M_1G concentration in colonic cancer tissue and in circulating white blood cells (WBC) before and after treatment.

V. Correlate M_1G concentration in colorectal cancer tissue with M_1G concentration in circulating WBC.

VI. Assess the Ki67 labeling index in normal and malignant tissues in at least 10 fields per section.

VII. Correlate COX-2 expression in colorectal cancer tissue with COX-2 expression in circulating WBCs.

VIII. Assess the toxicity profile of this drug.

OUTLINE: This is a two-stage nonrandomized, open-label study. Patients are assigned to 1 of 2 dose levels in stage 2.

STAGE I: Patients undergo an colorectal endoscopy. Patients whose biopsies confirm colorectal adenocarcinoma histology and require surgical resection continue on study stage 2.

STAGE II: Patients receive oral resveratrol on days 1-8. Patients undergo colorectomy on day 9. A tumor biopsy is performed during endoscopy and colorectomy for research purposes.

Two biomarkers of the potential activity of resveratrol are measured in nonmalignant and malignant colorectal tissue biopsy samples: levels of M_1G adducts by immunoslot blot analysis and levels of cyclooxygenase-2 protein/Ki67 by immunohistochemistry. Blood samples are collected at baseline and during colorectomy for analysis of resveratrol and its metabolites and other pharmacokinetic studies.

Resveratrol in Treating Patients With Colorectal Cancer That Can Be Removed By Surgery

Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics

National Cancer Institute (NCI)

Carcinoma, Hepatocellular

Liver Neoplasms

Liver Diseases

Hematinics

Liver Extracts

Resveratrol 1 gm po x 10 days prior to liver resection

Placebo

Brian G Harbrecht, MD

The purpose of this study is to determine if Resveratrol, a nutritional supplement, shows a beneficial effect in the cellular function of normal liver cells and diseased liver cells (cancer cells) in samples of liver tissue taken during elective liver surgery. Outcomes based on 3 measures will test the hypothesis that Resveratrol when used as a nutritional supplement will 1)improve metabolic function in liver cells, 2)reduce cellular growth and proliferation of cancer cells, 3)decrease inflammation in the liver.

Hepatic function will be assessed by standard laboratory techniques. Hepatocyte signaling pathway proteins will be measured using western blot analysis for protein expression and polymerase chain reaction for gene expression. Activation of signaling pathways in both native hepatocytes and carcinoma will be analyzed by multi-plex signal array. The effect on transcription factors that may be important in gene expression will be analyzed by transcription factor array. The effect of resveratrol in altering hepatocyte and cancer cell metabolism will be analyzed by proteomic analysis.

Resveratrol and Human Hepatocyte Function in Cancer

This outcome is a composite outcome and will be measured by assessing expression of multiple signaling proteins that are important in hepatic cell metabolism such as Akt, p38, Mitogen Activated Kinases, and Adenosine Monophosphate-activated Kinase (AMPK) and expression of gluconeogenic proteins such as Phosphoenolpyruvate carboxykinase (PEPCK).

This outcome is a composite outcome of cellular pathways important in cancer cell replication. This will be measured by the expression of genes and proteins that regulate hepatic cell growth/cell survival such as cyclin gene expression, expression of the tumor suppressor p53, and expression of apoptosis proteins Bcl-2 and Bcl-xl.

This outcome will be a composite outcome of pathways that regulate both cancer cell growth and inflammation. It will be measured by levels of genes and proteins for nitric oxide synthase, cytokines such as interleukin-6, and Nuclear Factor-kappa B signaling proteins.

University of Louisville

Dean E. Brenner, MD

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of resveratrol may prevent cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of resveratrol in preventing cancer in healthy participants.

OBJECTIVES:

* Determine the concentration of resveratrol and its metabolites in the plasma, urine, and feces of healthy participants.
* Correlate dose with systemic concentration of this drug and its metabolites in these participants.
* Determine the safety of this drug in these participants.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Beginning 5 days before study drug administration, participants are put on a controlled diet (avoiding all resveratrol-containing food or drink) for washout. Participants receive oral resveratrol once on day 1.

Cohorts of 10 participants receive escalating doses of resveratrol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 10 participants experience dose-limiting toxicity. A total of 16 participants are treated at the MTD.

Participants are followed at 2 and 7 days.

PROJECTED ACCRUAL: A total of 10-40 participants will be accrued for this study within 6 months.

UMCC 2003-064 Resveratrol in Preventing Cancer in Healthy Participants

Phase I Single-Dose Safety and Phamacokinetics Clinical Study of Resveratrol AKA IRB 2003-424

Blood and Lymph Conditions

Immune System Diseases

Lymphangioleiomyomatosis

Lymphangiomyoma

Perivascular Epithelioid Cell Neoplasms

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Anti-Infective Agents

Antineoplastic Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.

Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.

Patients will have been on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.

Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.

Nishant Gupta, MD

RESULT is a phase II dose-escalating, open-label, safety and efficacy study to determine if there is a potential benefit of resveratrol in combination with sirolimus in patients with lymphangioleiomyomatosis (LAM). The primary study objective is to assess the change in serum vascular endothelial growth factor-D (VEGF-D) level after 24 weeks of treatment with a combination of resveratrol and sirolimus as compared to the VEGF-D level in patients on a stable dose of sirolimus alone. The secondary objectives of this study include an assessment of the safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM, and to determine the effect of treatment with a combination of resveratrol and sirolimus on changes in lung function and quality of life.

Study Design RESULT was an open label, dose-escalation, phase 2 study with longitudinal repeated measures. In order to be eligible for trial inclusion, patients had to satisfy all of the following criteria: 1) confirmed diagnosis of LAM per the American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines14, 2) age ≥18 years with signed informed consent, 3) on sirolimus for at least 20 weeks, and 4) VEGF-D stabilization as demonstrated by two stable values post initiation of sirolimus and drawn at least 12 weeks apart from each other. Key exclusion criteria included inability to provide consent, active listing for lung transplantation, enrolled in another interventional clinical trial, known allergy or hypersensitivity to resveratrol, and current or planned pregnancy in the next six months.

RESULT was a single site study conducted at the University of Cincinnati (UC). Study enrollment was open to LAM patients throughout the United States with travel reimbursement provided through the study. The study was reviewed and approved by UC's Institutional Review Board (IRB 2016-4904). An independent Data and Safety Monitoring Board (DSMB) was convened and met every six months to ensure the safety of study participants. All subjects provided written informed consent prior to the conduct of any study related activity.

Outcome Measures The primary objective of this study was to assess the change in serum VEGF-D value after 24 weeks of treatment with a combination of resveratrol and sirolimus, as compared to the historical VEGF-D values of patients prior to the study on sirolimus alone. Serial assessments of serum VEGF-D, pulmonary function tests (PFTs), treatment related adverse effects (AEs), complete blood count, liver and renal function tests, and HRQOL were performed at baseline and at 8, 16, and 24 weeks. In addition, sirolimus trough levels, measured 24 +/- 4 hours following the last dose, were assessed at baseline and at weeks 2, 4, 8, 12, 16, 18, 20 and 24. VEGF-D quantification was performed at the Translational Trial Development and Support Laboratory based at Cincinnati Children's Hospital Medical Center in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) approved manner. All other laboratory assessments were performed via Quest Diagnostics. HRQOL was measured by using four validated scales: St. George's Respiratory Questionnaire (SGRQ), University of California San Diego Shortness of Breath score (SDSOB), EuroQol visual analogue scale (EQVAS), and A Tool to Assess Quality of Life in LAM (ATAQ-LAM).

Study Drug Resveratrol used in this study was obtained from Evolva and manufactured by fermentation using genetically modified yeast in a process that results in trans-resveratrol with a purity of at least 98%, and packaged into capsules with each capsule containing 125mg resveratrol. The capsules were independently verified for content by mass spectrometry performed at UC and for sterility by microbial testing at Q Laboratories Inc., Cincinnati. Investigational new drug (IND) designation for studying Resveratrol in this trial was obtained from the United States Food and Drug Administration (FDA): IND 131722; IND Sponsor: N. Gupta.

Resveratrol was administered in a stepwise dose escalating fashion at 8-week intervals with assessment of VEGF-D, PFTs, AEs, and HRQOL prior to each dose escalation. The starting dose of resveratrol was 250mg once daily for the first 8 weeks, followed by 500mg daily from Weeks 8 - 16, and 500mg twice daily for the last 8 weeks (Weeks 16 - 24), with provisions for dose reduction if necessitated by AEs. Treatment related AEs were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.

LAM is a disease that almost exclusively involves females. Thus trial participants will be females only.

Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial

Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial (RESULT)

Change in serum VEGF-D level in pg/ml after treatment with a combination of resveratrol and sirolimus as compared to the historical VEGF-D level in patients on a stable dose of sirolimus alone. Baseline VEGF-D values represent serum VEGF-D levels on stable dose of sirolimus alone prior to starting study drug.

Safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM

Difference in the absolute Forced expiratory volume in one-second (FEV1) after 24 weeks of treatment. FEV1 values reported are in liters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Higher FEV1 scores indicate better lung function.

Quality of life scores will be calculated by using SGRQ to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM. This is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating worse quality of life.

Quality of life scores will be calculated by using ATAQ-LAM to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM. A Tool to Assess Quality of Life in LAM (ATAQ-LAM) is a disease-specific instrument designed to assess HRQOL in patients with LAM, and consists of 32 items divided into 4 domains: exertional dyspnea, cough, fatigue, and emotional well-being. The total scores on this scale can range between 32 - 192, with higher scores indicating worse quality of life.

The San Diego shortness of breath questionnaire measures the quality-of-life impairment secondary to dyspnea resulting from pulmonary disorders. It is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living, with higher scores indicating worse quality of life.

The EuroQOL visual-analogue scale (EQVAS) measures self-reported ratings of health status. Scores range from 0 to100, with lower scores indicating worse functioning.

National Heart, Lung, and Blood Institute (NHLBI)

University of Cincinnati

Adjunct Assistant Professor

Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.

250mg resveratrol added to pre-existing sirolimus

250mg Resveratrol Daily (First 8 Weeks)

500mg resveratrol added to pre-existing sirolimus

500mg Daily Resveratrol (Weeks 8 - 16)

1,000mg resveratrol added to pre-existing sirolimus

1,000mg Daily Resveratrol

Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.

Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.

Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.

Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.

Treatment Arm

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline VEGF-D level in patients on a stable dose of sirolimus alone

Week 8

Week 16

Week 24

Longitudinal slope of serum VEGF-D levels

Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels After Treatment With a Combination of Resveratrol and Sirolimus as Compared to Baseline Serum VEGF-D Levels on Sirolimus Alone

250 mg daily

500mg daily

1000mg daily

Number of Treatment-Emergent Adverse Events

Baseline

Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus

St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus

Scores on "A Tool to Assess Quality of Life in LAM (ATAQ-LAM) Quality of Life Assessment" Scale After Treatment With 24 Weeks of Resveratrol and Sirolimus

San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus

EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.

First 8 Weeks (250mg Daily Resveratrol)

Weeks 8 - 16 (Resveratrol 500mg Daily)

Weeks 16-24 (Resveratrol 1,000mg Daily)

Herbal and Botanical

Grape

Cola

GM-CSF administration to all subjects in addition to chemotherapy treatment.

Patients were randomly assigned to one of four dose cohorts: plant-derived resveratrol tablets (purchased through the Life Extension Foundation, Scottsdale, AZ) at a dose of 80 mg/day, plant-derived resveratrol tablets at a dose of 20 mg/day, Grape Powder (GP) dissolved in water and taken orally (supplied by the California Table Grape Commission) at a dose of 120 g/day, and GP at a dose of 80 g/day.

Randall Holcombe, MD

Resveratrol is purported to possess cancer preventive activity, especially for colon cancer, though its mechanisms of action are not well defined. Resveratrol is found in the skin of grapes and has anti-oxidative and pro-apoptotic effects on cancer cell lines in vitro. The main dietary sources of resveratrol are grapes, grape products, and red wine, and small amounts may be found in mulberries. A prior report and compelling preliminary data from our laboratory suggest that resveratrol modulates Wnt signaling, a signaling pathway which is activated in over 85% of colon cancers. In this proposal, studies were performed to define the actions of resveratrol on the Wnt signaling pathway in a clinical trial in which patients with colon cancer received treatment with Resveratrol, and correlative laboratory studies examined its effects directly on colon cancer and normal colonic mucosa. These studies provided data on the mechanisms of resveratrol action and provided a foundation for future prevention trials, correlative studies and therapeutic clinical research with this agent.

Patients will be treated with a two-week course of resveratrol. The initiation of the treatment will be approximately 14 days before standard of care surgical resection of tumor. Resveratrol will be ingested as 20 mg pills or in the form of freeze-dried grape extract which is prepared by the California Table Grape Commission used under GMP guidelines for human consumption.

The first two patients receiving resveratrol will be treated at a dose of 20 mg/day, the third and fourth patients at a dose of 80 mg/day, and the fifth and sixth patients with a dose of 160 mg/day. All patients receiving grape extract will receive 125 mg/day that will have to be mixed with one 8 oz glass of water. There will be no dose adjustments. If a patient has any side effects which are attributed to the resveratrol, it will be discontinued.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors	NCT01476592	Neuroendocrine ...	Resveratrol	18 Years -	University of Wisconsin, Madison
Resveratrol in Treating Patients With Colorectal Cancer That Can Be Removed By Surgery	NCT00433576	Adenocarcinoma ... Adenocarcinoma ... Stage I Colon C... Stage I Rectal ... Stage II Colon ... Stage II Rectal... Stage III Colon... Stage III Recta...	resveratrol pharmacological... laboratory biom...	18 Years -	National Cancer Institute (NCI)
A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors	NCT01476592	Neuroendocrine ...	Resveratrol	18 Years -	University of Wisconsin, Madison
Resveratrol and Human Hepatocyte Function in Cancer	NCT02261844	Liver Cancer	Resveratrol Placebo	21 Years - 80 Years	University of Louisville
UMCC 2003-064 Resveratrol in Preventing Cancer in Healthy Participants	NCT00098969	Unspecified Adu...	resveratrol	18 Years - 80 Years	National Cancer Institute (NCI)
Resveratrol and Human Hepatocyte Function in Cancer	NCT02261844	Liver Cancer	Resveratrol Placebo	21 Years - 80 Years	University of Louisville
Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial	NCT03253913	Lymphangioleiom...	Sirolimus Resveratrol	18 Years -	University of Cincinnati
Resveratrol for Patients With Colon Cancer	NCT00256334	Colon Cancer Cancer	Resveratrol	18 Years -	University of California, Irvine

Spots Global Cancer Trial Database for resveratrol

Every month we try and update this database with for resveratrol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for resveratrol

Every month we try and update this database with for resveratrol cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for resveratrol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.