A Molecular Pharmacodynamic Dose-titration Trial of Conjugated Linoleic Acid (CLA; Clarinol®) in Patients With Advanced Solid Tumors

Inclusion Criteria

A subject is eligible for inclusion in this study only if all of the following criteria apply:

1. Written informed consent.
2. Age 18 years or more.
3. Performance status of 0, 1, or 2 on the Eastern Co-operative Oncology Group (ECOG) Scale.
4. A predicted life expectancy of at least 3 months, in the estimation of the investigator.
5. Subjects with histologically or cytologically confirmed advanced solid tumors, who have failed conventional therapy for their tumor type or have a tumor type for which no standard effective therapy exists.
6. At least 4 weeks since last chemotherapy, radiotherapy, biologic therapy or surgery. Subjects must be free of post-treatment side effects. No concurrent chemotherapy, biologic therapy or radiotherapy is allowed.
7. Hematological/clinical chemistry criteria of:

   Hemoglobin ≥ 9.0 g/dL WBC ≥ 3,500/mm3 \[≥ 3.5 x 109/L\] Neutrophils ≥ 1,500/mm3 \[≥ 1.5 x 109/L\] Platelets ≥ 100,000/mm3 \[≥ 100.0 x 109/L\] Calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault Formula.
8. Serum bilirubin \< 2.0 mg/dL (34 µmol/L)
9. SGOT/AST, SGPT/ALT and alkaline phosphatase \< 2 times the upper limit of normal if liver metastases cannot be visualized by abdominal computed tomography (CT) or magnetic resonance imaging (MRI scan). If liver metastases are present, subjects with \< 5 times the upper limit of normal are eligible to participate.
10. Once the RP2D is established, additional patients enrolled at the expanded dose cohort must have tumor that is accessible to two serial biopsies and that is documented (by IHC or RT-PCR) to express S14.

Exclusion Criteria

A subject is ineligible if any of the following criteria apply:

1. Cancer cachexia, defined by the combination of: unintentional weight loss ≥10%, low

   caloric intake (≤ 1500 kcal/day), and systemic inflammation (C-reactive protein ≥ 10mg/L).\[52\]
2. Type II diabetes mellitus
3. Women who are pregnant or lactating, or women subjects of childbearing potential who refuse to practice adequate contraception. (oral contraceptives or IUD; double barrier such as diaphragm plus spermicide; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner of that female). Childbearing potential is defined as women who are not surgically sterilized (i.e. have not had a hysterectomy, bilateral oophorectomy \[ovariectomy\], or bilateral tubal ligation) or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study).
4. Men unwilling to abstain from sex or use effective contraception during the study.
5. Subjects with uncontrolled emesis, regardless of etiology.
6. Active infection, or seropositivity for HIV or Hepatitis B/C.
7. Subjects with clinical evidence of any gastrointestinal (GI) conditions (i.e., removal of a portion of the stomach, recent GI obstruction or GI neuropathy) or subjects taking drugs that would alter GI absorption or motility (e.g., cisapride).
8. Intercurrent severe medical problems, which would significantly limit full compliance with the study or expose the subject to unnecessary risk.