A Phase II Multicenter, Randomized, Placebo Controlled, Double Blinded Clinical Study of KD018 as a Modulator of Irinotecan Chemotherapy in Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

1. Patients with histologically confirmed metastatic colorectal cancer (mCRC), who have
received and/or progressed on a prior oxaliplatin-based chemotherapy regimen.

2. Patients must have been off of chemotherapy for at least 4 weeks prior to signing the
informed consent/start of screening.

3. Patients with wild-type or mutant KRAS mCRC.

4. At least one measurable lesion by RECIST 1.1.

5. ECOG PS Performance Status 0-2.

6. Must be >/=18 years of age.

7. Expected survival of at least 6 months.

8. Women of child-bearing potential (i.e., women who are pre-menopausal or not
surgically sterile) must use acceptable contraceptive methods (abstinence,
intrauterine device [IUD], oral contraceptive or double barrier device), and must
have a negative serum or urine pregnancy test within 1 week prior to beginning
treatment on this trial. Nursing patients are excluded. Sexually active men must also
use acceptable contraceptive methods. Pregnant and nursing patients are excluded
because the effects of the combination of KD018 and irinotecan on a fetus or nursing
child are unknown.

9. Must be able and willing to give written informed consent.

10. Patients must have the following clinical laboratory values:

1. ANC count >/= 1,500/ mm3.

2. Platelets >/= 100,000/ mm3.

3. Hemoglobin >/= 9 gm/dL (may be corrected by transfusion).

11. Evidence of adequate hepatic function, Bilirubin < 1.5 x upper limit of normal (ULN)
AST be has tumor involvement. (Note, if both AST and ALT are done, both must be ULN)

12. Serum creatinine
13. Serum potassium within institutional limits of normal (may be corrected with
potassium repletion).

Exclusion Criteria:

1. Continued treatment with bevacizumab with documented evidence of disease progression
on a bevacizumab-containing regimen.

2. Uncontrolled or symptomatic brain metastasis.

3. Serious concomitant systemic disorders (e.g., active infection) that, in the opinion
of the investigator, would compromise the safety of the patient or compromise the
patient's ability to complete the study.

4. Unwilling or unable to follow protocol requirements or to give informed consent.

5. No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning
treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks
must have elapsed from any prior surgery, radiation, hormonal or other drug therapy
for their cancer.

6. Known HIV positivity, as safety in this patient population has not been assessed.

7. Presence of metastatic disease that, in the opinion of the investigator, would
require palliative treatment within 4 weeks of enrollment.

8. Altered mental status precluding understanding of the informed consent process and/or
completion of the necessary studies.

9. Pregnant or breast-feeding women.

10. Men and women of childbearing age and potential, who are not willing to use effective
contraception.

11. Major surgery within the previous 4 weeks.

12. Patients taking concurrent medications of any kind which are strong inducers or
inhibitors of CYP3A4.

13. Patients previously treated with an irinotecan-containing regimen.