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

Inclusion Criteria:

- Subjects must have a histological diagnosis of cancer with an elevated baseline
plasma IL-6 level (>3.0 pg/mL) as determined by Dr. Lilly's laboratory.

- 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