Phase I Assay-guided Trial of Anti-inflammatory Phytochemicals in Patients With Advanced Cancer

This study is for subjects with solid cancers (gastrointestinal, lung, breast, prostate, lymphoma or cancer of the lymph nodes). The overall goal of this study is to identify plant-derived phytochemicals that can safely reduce systemic inflammation (inflammation throughout the entire body) in subjects with advanced cancer.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: Grape Seed Extract; Drug: Vitamin D

Detailed Description

This study will look at oligomeric procyanidin complex (OPC) and vitamin D3. OPC is the major part of Grape Seed Extract (GSE). Researchers are in looking at the combination of GSE and vitamin D in subjects with solid cancers (gastrointestinal, lung, breast, prostate, lymphoma or cancer of the lymph nodes). Researchers will examine the safety of the GSE and vitamin D when GSE is given at different doses. Researchers will also look at the effects of GSE and vitamin D on your quality of life and your body. In particular, they will look at differences in biomarkers in your blood and urine.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a histological diagnosis of cancer
• Subjects must be 21 or more years of age
• Subjects must have metastatic or locally advanced, unresectable cancer. Cancer must be "active" (i.e. demonstrable by physical examination, blood tests, or radiographical procedures).
• Subjects may not initiate a new form of cancer therapy, non-steroidal or steroid anti-inflammatory agents, or antibiotics during the study period or for 4 weeks prior to the start of study agents.
• Subjects must be able to give written consent to the study.
• Subjects must have adequate hematologic, renal, and hepatic function at baseline, as follows:
• Hematology parameters: ANC >1500/mcL, platelets > 100,000/mcL, Hgb >8.0gm/dL
• Renal Function: Creatinine <1.8mg/mL
• Liver Function: Total bilirubin ≤ULN, AST and ALT <1.5xULN, Alk phosphatase <2.5xULN
• Subjects must have normal serum phosphate and serum calcium levels:
• Serum Phosphate > 2.3 and < 4.8 mg/dL
• Serum Calcium > 8.5 and < 10.5
• Subjects may be receiving anti-cancer treatment, but this treatment should be have been instituted at least 4 weeks prior to enrollment, and may not change during the study period.

Exclusion Criteria:

• Uncontrolled cancer requiring the institution of new anti-cancer therapy during the study period.
• Presence of any severe or uncontrolled concurrent medical condition which, in the opinion of the investigator, would increase the risk of serious toxicity from the study drugs.
• Any uncontrolled systemic inflammatory disease or infection requiring antibiotics, non-steroidal, or steroidal anti-inflammatory agents.
• Initiation of strong antioxidant supplements during treatment, or ongoing use of supplements containing concentrated plant-derived polyphenols (pine bark, grape seed, green tea, milk thistle extracts; resveratrol; ellagic acid)
• Pregnancy or breast feeding
• Any history of allergies to grapes or grape seed.
• Current treatment with lenalidomide, thalidomide, imipquimod, interferon, cytokines (G-CSF, GM-CSF, IL-1Rα), TNFα antagonists, or Lithium.
• History of sarcoidosis
• History of hypercalcemia
• Use of any non-protocol vitamin D supplementation.
• Uncontrolled hypertension
• Current treatment with warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Grape Seed Extract and Vitamin D; All patients will take Grape Seed Extract from Day 1 to Day 21. All patients will take Grape Seed Extract and Vitamin D together from Day 22 until Day 64. For all patients on the study, patients will take Vitamin D once a day at a dose of 4000IU.	Drug: Grape Seed Extract; All patients enrolled to the study will take Grape Seed Extract alone for 21 days.; Other Names: GSE; Drug: Vitamin D; From Day 22 until Day 64 of the study, patients will take Grape Seed Extract and Vitamin D together. Patients will take Vitamin D once at a day at 4000 IU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximally-tolerated dose of Grape Seed Extract in Patients with Solid Tumors	Decisions to escalate or expand a dose level will be based only on the GSE-only treatment period (day 1-21). To be evaluable for toxicity, a patient must receive at least 3 weeks of GSE treatment, or have experienced dose-limiting toxicity (DLT). All patients enrolled are to be fully followed for toxicity, but any patients who are not evaluable for toxicity will be replaced.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL6 Response	Plasma IL-6 levels before and after 21 days and 63 days of GSE treatment will be quantified to estimate the dose response relationship between GSE dose and reduction in inflammation.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Other Inflammatory Markers	Other markers that will be measured will include serum CRP, albumin, AGEs (advanced glycation end products), rAGE (soluble receptor for AGEs), 25-OH-vitamin D3, and urine for oxidative damage DNA biomarkers (urinary 8-oxoGua and 8-oxodG). Correlations between dose and change in these parameters from before to 21, 63 days after start of GSE dosing will be described.	2 years
Quality of Life Questionnaires	Serial QOL assessments will be made by the FACT series of QOL questionnaires	2 years
Effect of Vitamin D3 on Anti-Inflammatory Effects of GSE	The ability of a fixed dose of vitamin D3 (4000 IU daily) to further suppress IL-6 levels in subjects on GSE treatment will be evaluated.	2 years

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Michael Lilly, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 25, 2013
• First Submitted That Met QC Criteria: March 25, 2013
• First Posted (Estimate): March 28, 2013

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Micronutrients; Vitamins; Bone Density Conservation Agents; Antioxidants; Vitamin D; Grape Seed Extract
• Other Study ID Numbers: 101839