Randomized, Active-Controlled, Open-Label Phase 2 Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy

Inclusion Criteria:

- Metastatic CRC that has progressed following first-line therapy.

- Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST], Version
1.0.34.

- Male or female = 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status = 2.

- Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE,
Version 3.0, grade = 1.

- Adequate organ and bone marrow function as evidenced by:

- Hemoglobin = 9 g/dL (transfusion and/or growth factor support allowed)

- Absolute neutrophil count (ANC) = 1.5 x 109/L

- Platelet count = 100 x 109/L Serum creatinine = 1.5 x the upper limit of normal
(ULN) or creatinine clearance = 60 mL/min

- Aspartate aminotransferase (AST) and alkaline phosphatase = 2.5 x ULN in
subjects with no liver metastasis and = 5.0 x ULN in subjects with liver
metastasis

- Total bilirubin = 1.5 x ULN

- Women of childbearing potential must be willing to consent to using effective
contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with
spermicide, intrauterine device) while on treatment and for at least 3 months
thereafter. Men who are the partner of a woman of childbearing potential must be
willing to consent to using effective contraception (e.g., vasectomy or barrier with
spermicide) while on treatment and for 3 months thereafter.

- All female subjects of childbearing potential must have a negative pregnancy test
(serum or urine) result before initiating study treatment.

- Subjects must be fully informed about their illness and the investigational nature of
the study protocol (including foreseeable risks and possible side effects) and must
sign and date an IEC- or IRB-approved ICF (including HIPAA authorization, if
applicable) before performance of any study-specific procedures or tests.

- Subjects must be willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.

Exclusion Criteria:

- First-line treatment with an irinotecan-based regimen (eg, FOLFIRI).

- Anticipation of need for a major surgical procedure or radiation therapy (RT) during
the study.

- Treatment with chemotherapy, other TZDs, RT, surgery, immunotherapy, biological
therapy, or any investigational anticancer agent within 4 weeks before start of study
treatment.

- History of any of the following conditions within 6 months before initiating study
treatment:

- Diabetes mellitus requiring treatment with insulin or TZD agents

- Myocardial infarction with significant impairment of cardiac function (e.g.,
ejection fraction = 50%)

- Severe/unstable angina pectoris

- Coronary/peripheral artery bypass graft

- New York Heart Association (NYHA) class III or IV congestive heart failure

- Malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel
disease, or partial bowel obstruction.

- Subjects with clinically active brain metastases (defined as untreated, symptomatic,
or requiring therapy with steroids or anticonvulsants to control associated
symptoms); uncontrolled seizure disorder; spinal cord compression; or carcinomatous
meningitis. Subjects with treated brain metastasis will be included in the study if
they have recovered from the acute, toxic effects of RT. A minimum of 15 days must
have elapsed between the end of RT and enrollment into the study.

- History of malignancy other than CRC, unless there is an expectation that the
malignancy has been cured, and tumor-specific treatment for the malignancy has not
been administered within the previous 5 years.

- Clinically significant, severe, active infection requiring IV antibiotic or antiviral
agents.

- Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement
with the tumor. Subjects with minimal pleural effusion may be eligible upon request
by Investigator and approval by Sponsor.

- Need for concomitant use of other TZDs during the study.

- Previous administration of CS-7017.

- Pregnant or breast feeding.

- Known to be homozygous for the UGT1A1*28 allele.

- Known history of severe hypersensitivity reactions to any of the components of
CS-7017, irinotecan, leucovorin, or 5-FU.

- Serious intercurrent medical or psychiatric illnesses or any other conditions that in
the opinion of the Investigator would impair the ability to give informed consent or
unacceptably reduce protocol compliance or safety of the study treatment.