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

CPX-1 Liposome Injection is a liposomal formulation of a fixed combination of the antineoplastic drugs irinotecan HCl and floxuridine. The two drugs are present inside the liposome in a fixed 1:1 molar ratio. CPX-1 was developed as a means of delivering and preserving a fixed 1:1 molar ratio of the two drugs. This ratio was found in vitro and in vivo models of cancer to have synergistic anti-cancer activity and preservation and delivery of this ratio is important because other ratios of these two drugs have been found to be antagonistic or only additive. Both floxuridine and irinotecan HCl are active chemotherapeutic agents, each approved for clinical use in the United States and Canada for colorectal cancer. Current practice routinely administers 5- fluorouracil with irinotecan in combination regimens in first or second line treatment without the means of preserving the synergistic ratio.

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.