Multicenter Study Of CPX-1 (Irinotecan HCl: Floxuridine) Liposome Injection In Patients With Advanced Colorectal Cancer

Inclusion Criteria

• Ability to understand and voluntarily sign an informed consent form
• Age > 18 years at the time of signing the informed consent form
• Histological confirmation of advanced stage, primary or metastatic colorectal carcinoma
• Prior therapy (Group 1, irinotecan naive):
• No more than one regimen for metastatic disease
• No more than two regimens overall; one for neoadjuvant/adjuvant and one for metastatic/advanced disease
• Prior therapy (Group 2, irinotecan refractory):
• Disease progression on or within 3 months after prior irinotecan-containing regimen
• CPX-1 treatment must start within 6 months after documentation of disease progression on irinotecan (other therapies are permitted after irinotecan and before study entry)
• Must have measurable disease as defined by RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Able to adhere to the study visit schedule and other protocol requirements
• Life expectancy of at least 24 weeks
• Laboratory values fulfilling the following:
• Absolute neutrophil count (ANC) >1500 cells/mm3 (1.5 x 109/L)
• Platelet count > 100, 000/mm3 (100 x 109/L)
• Serum creatinine <1.5 x upper limits of normal (ULN)
• Serum SGOT/AST and SGPT/ALT <3 x upper limits of normal (ULN) (<5 times ULN if caused by liver metastases)
• Serum total bilirubin < 1.25 x upper limits of normal (<2 times ULN if caused by liver metastases)
• All men and women must agree to practice effective contraception during the study period and for three months afterward if not otherwise documented to be infertile.
• Prior radiation therapy must be completed at least 4 weeks prior to enrollment and the patient recovered from any toxicity related to the radiation therapy.

Exclusion Criteria

• Prior treatment with irinotecan or an irinotecan-containing regimen (Group 1 only)
• Intolerant of an irinotecan-containing regimen (Group 2 only)
• Without documented evidence of irinotecan-refractoriness (Group 2 only)
• Chemotherapy or investigational anticancer therapeutic drugs in the four weeks prior to study entry.
• Hypersensitivity to irinotecan, floxuridine or liposomal products.
• History of Wilson's disease or other copper-related disorder.
• Clinically significant cardiac disease (New York Heart Association Class III or IV).
• Severe debilitating pulmonary disease.
• Active infection requiring continuing intravenous antibiotic treatment; recent infections must have resolved at least 5 days
• Severe or active enteropathy or recurrent onset of diarrhea, defined as an excess of 2 to 3 stools above the normal daily rate within the past four weeks.
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating women. Continued use of a drug or other product known to induce or inhibit CYP3A4. ---Patients must discontinue these products for at least 2 week prior to enrollment.