Curcumin in Combination With 5FU for Colon Cancer

Confirm clinical safety and identify clinical response rate of combination treatment with
curcumin and 5FU in chemorefractory CRC patients. To determine whether curcumin
administration induces systemic alterations in inflammatory and epigenetic biomarkers in
patients with chemoresistant metastatic colorectal cancer (CRC). To correlate altered
biomarker findings with clinical response according to RECIST V1.1 and survival criteria.

Inclusion Criteria:

- Male or female 18 years or older, at the time of signing the informed consent.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Histologically or cytologically confirmed diagnosis of metastatic colorectal cancer
that is not response to standard 5FU based therapies.

- Performance Status (PS) score of 0 to 2 according to the Eastern Cooperative Oncology
Group (ECOG) scale.

- Able to swallow and retain oral medication.

- A female subject is eligible to participate if she is of:

- Non-childbearing potential defined as pre-menopausal females with a documented tubal
ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous
amenorrhea (in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) >40 mili-internation unit (MIU)/ml and estradiol <40 pg/ml
(140pmol/L) is confirmatory

- Child-bearing potential and agrees to use a contraception method of abstinence,
intrauterine device (IUD), barrier methods or birth control pills prior to the start
of dosing to sufficiently minimize the risk of pregnancy at that point and until
three months after the last dose of the study medication.

- Male subjects must agree to use a method of contraception. This criterion must be
followed from the time of the first dose of study medication until three months after
the last dose of study medication.

- Adequate organ system function defined as follows:

System Laboratory Values Hematologic Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
Hemoglobin ≥ 9.5 g/dL Platelets ≥ 75 x 10^9/L For subjects not on warfarin-based
anticoagulants: Prothrombin time/International normalized ratio (PT/INR) and partial
thromboplastin time (PTT) ≤ 1.1x upper limit of normal (ULN) INR (subjects on
warfarin-based anticoagulant): 2-3 x ULN Hepatic Total bilirubin ≤ 1.5x ULN (isolated
bilirubin > 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <
35%) Aspartate aminotransferase (AST) and alanine transaminase (ALT) 1 ≤ 1.5x ULN Albumin
≥ 2.5 g/dL Renal Creatinine ≤ ULN; or Calculated creatinine clearance2 ≥ 50 mL/min; or
Metabolic Fasting Serum Glucose < 250 mg/dL Cardiac Left Ventricular Ejection fraction
(LVEF) ≥ lower limit of normal (LLN) by echocardiogram (ECHO) Blood pressure Systolic <
160 mm Hg and Diastolic < 100 mm Hg.

1. If liver metastases are present, AST and ALT ≤ 2.5x ULN is permitted

2. As calculated by Cockcroft-Gault formula.

Exclusion Criteria:

- Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including
investigational drugs within 28 days or 5 half-lives, whichever is shorter prior to
the first dose of any one of the investigational drugs described in this study.

- Unresolved toxicity by National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events, Version 4.0 (NCI-CTCAE V4) of > Grade 1 from previous anti-cancer
therapy.

- Presence of active GI disease or other condition that could affect gastrointestinal
absorption (malabsorption syndrome) or predispose a subject to GI ulceration.

- Evidence of mucosal or internal bleeding

- Any major surgery within the last four weeks

- Uncontrolled diabetes mellitus

- Any malignancy related to human immunodeficiency virus (HIV), known history of HIV,
history of known Hepatitis B virus (HBV) surface antigen positivity (subjects with
documented laboratory evidence of HBV clearance may be enrolled) or positive
Hepatitis C virus (HCV) antibody.

- Known active infection requiring parenteral or oral anti-infective treatment.

- Subjects with brain metastases are excluded if their brain metastases are:

- Symptomatic

- Treated (surgery, radiation therapy) but not clinically and radiographically stable
one month after therapy (as assessed by at least 2 distinct contrast enhanced MRI or
CT scans over at least a one month period), or

- Asymptomatic and untreated but > 1 cm in the longest dimension

- History or evidence of current clinically significant uncontrolled arrhythmias.

- Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are
eligible.

- History of acute coronary syndromes (including unstable angina), myocardial
infarction, coronary angioplasty, or stenting or bypass grafting within six months of
screening.

- Class II, III, or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system.

- Any serious or unstable pre-existing medical, psychiatric, or other condition
(including lab abnormalities) that could interfere with subject's safety or providing
informed consent.

- Known immediate or delayed hypersensitivity to any of the components of the study
treatment(s).

- Evidence of severe or uncontrolled systemic diseases (unstable or uncompensated
respiratory, hepatic, renal, or cardiac disease, including unstable hypertension).

- Pregnant or lactating females.