An Open Label Phase II Study of Indisulam in Combination With Irinotecan in Patients With Metastatic Colorectal Cancer Who Have Been Previously Treated With 5-Fluorouracil/Leucovorin and Oxaliplatin

Patients with the following characteristics will not be included in the study:

More than three previous lines of chemotherapy (including neo-adjuvant and adjuvant)

Prior treatment with cytotoxics other than 5- fluorouracil/leucovorin (capecitabine and UFT are permitted) and oxaliplatin. Prior epidermal growth factor receptor targeted and anti-angiogenic therapy is permitted.

Untreated brain metastases (patients who have been treated for CNS metastases must be asymptomatic and radiologically stable for 4 weeks prior to entry). Patients must not have clinical symptoms from brain metastases and must not be taking corticosteroids for the treatment of brain metastases. Patients must not have leptomeningeal metastases

Any of the following laboratory parameters:

1. hemoglobin \<10 g/dl;

2. neutrophils \<1.5 x 109/L;

3. platelets \<100 x 109/L;

4. serum bilirubin \>25 mmol/l (1.5 mg/dl);

5. other liver parameters \>2.5 x upper normal limit (ULN) (\> 5 x upper normal limit in the presence of hepatic metastases);

6. serum creatinine \>1.5 x ULN;

7. serum calcium (corrected for albumin) \>=11.5 mg/dl. 5. History of Gilbert's Disease or conjugated hyperbilirubinemia 6. Concurrent or previous malignancy of a different tumor type within five years of starting the study except for adequately treated non- melanoma skin cancer or cervical intraepithelial neoplasia

Uncontrolled infections

Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start

Chronic inflammatory bowel disease and/or bowel obstruction

History of hypersensitivity to sulfonamides

History of severe hypersensitivity reactions to one of the excipients of irinotecan

Treatment within two weeks before the start of the stud y with any of the following: coumarin anti-coagulants, terfenadine, cisapride, cyclosporin, tacrolimus, theophylline, diazepam, sulphonylurea hypoglycaemics, phenytoin, or carbamazepine

Any treatment with investigational drugs within 30 days before the start of the study

Pregnancy or lactation (all women of childbearing potential must have a negative pregnancy test before inclusion in the study; post-menopausal women must be amenorrheic for at least 12 months). Female patients must use adequate contraceptive protection

Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection

History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance.

Legal incapacity

What this study is about