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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: Grape Seed Extract
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Grape Seed Extract and Vitamin D<br>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<br>* All patients enrolled to the study will take Grape Seed Extract alone for 21 days.<br>* Other names: GSE;Drug: Vitamin D<br>* 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.<br>|

What is the study measuring?
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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 |