CPX-1 and Colorectal Cancer
CPX-1 (Irinotecan HCl:Floxuridine) Liposome Injection
CPX-1 Liposome Injection is a liposomal formulation of a synergistic 1:1 molar ratio of irinotecan HCI and floxuridine. Irinotecan and floxuridine is a drug regimen that has proven activity in the treatment of cancer, particularly against GI tumors. Both drugs are approved for the treatment of colorectal cancer. CPX-1 is currently in a Phase 2 clinical trial as a potential treatment for patients with colorectal cancer. Colorectal cancer represents the first of numerous tumor types where CPX-1 may provide a benefit to patients.
Ongoing Clinical Trials
There are currently no open clinical trials with CPX-1.
CPX-1 represents a new approach to treatment, where synergistic molar ratios of combined drugs are encapsulated in a drug delivery vehicle in order to deliver and maintain the desired ratio following administration. CPX-1 is a liposomal formulation of irinotecan HCl:floxuridine locked in a synergistic 1:1 molar ratio. CPX-1 is administered intravenously as a 90 minute infusion every two weeks.
The use of irinotecan in combination with a fluoropyrimidine (such as floxuridine) is a frequently used combination for the treatment of patients diagnosed with advanced colorectal cancer (CRC). This combination may offer a benefit in patients with other forms of cancer, such as other gastrointestinal cancers.
A Phase 1 dose escalation study in 33 patients with advanced solid tumors (15 of the 33 patients had CRC) has been completed with CPX-1. Data from the Phase 1 study were first presented at the 2006 American Society of Clinical Oncology meeting. Based on the safety and efficacy seen in the Phase 1 study, Celator conducted a Phase 2 study in 59 patients with advanced CRC (26 patients were irinotecan-naïve and 33 patients were irinotecan-refractory). Data from the Phase 2 study were presented at the 2008 American Society of Clinical Oncology meeting with additional information presented at the 10th World Congress on Gastrointestinal Cancer in 2008.
Celator is seeking a partner / external collaborator to further the clinical development of CPX-1.
Celator has studied the ratio dependence of irinotecan and floxuridine in 11 tumor cell lines. According to this research, irinotecan and floxuridine delivered in a 1:1 molar ratio is generally found to deliver a synergistic benefit, while the same agents in a 10:1 molar ratio are shown to be antagonistic, particularly in colorectal cell lines. These drugs are currently administered in clinical practice without regard to drug ratios. Because they have different pharmacokinetic properties, when combined these drugs will be distributed independently and at different rates. CPX-1 combines irinotecan HCI and floxuridine in a synergistic ratio incorporated into a delivery technology able to maintain that ratio after administration to patients. In preclinical studies, a 1:1 ratio of irinotecan HCI and floxuridine in an unbridled drug cocktail where the drug ratio is not locked has been found to be only somewhat effective in killing cancer cells. By using a liposome-based delivery mechanism developed from the CombiPlex technology platform, CPX-1 is able to lock in and maintain irinotecan HCI and floxuridine in a 1:1 ratio. Clinical results thus far indicate that CPX-1 produces a significant increase in therapeutic activity when compared to an unbridled cocktail of irinotecan HCI and floxuridine. Below is an illustration of the activity of the irinotecan:floxuridine combination in a mouse model of colorectal cancer. This compares the uncontrolled drug ratio to a locked CPX-1 formulation and also to saline. In this example, the drug ratio maintained by CPX-1 was considerably more effective than the uncontrolled cocktail, even when administered at one-half the dose.
NOTE: In the above model, the tumor eventually re-grows because treatment was not continued.
Celator conducted a Phase I clinical study involving 33 patients with heavily pre-treated, advanced solid tumors. The intended 1:1 molar ratio of irinotecan HCI and floxuridine was maintained in plasma and both drugs were bioavailable as indicated by the presence of their metabolites (SN-38 and 5-FU) in plasma of all subjects. Adverse events were predictable, dose-related and qualitatively similar to conventional irinotecan and fluoropyrimidine regimens. In this dose-escalating study, 73 percent of patients showed clinical benefit, including either partial tumor regression or stable disease. In 10 of the 33 patients studied, delay of disease progression was greater than six months.
Fifteen of the 33 patients in the Phase 1 study had advanced colorectal cancer. The response rate in this subset of patients was 13% (patients had partial remissions) and disease control was 73% with a median progression-free survival of 5.4 months. These data appear superior to treatment involving irinotecan alone or irinotecan in combination with 5-FU and leucovorin (FOLFIRI) as reported in the literature in this patient population.
Based on these promising clinical results, CPX-1 was advanced into a Phase 2 study in patients with colorectal cancer.
Learn more about the Phase 2 study for CPX-1.
According to the American Cancer Society, colorectal cancer is the third most common cancer found in both men and women in the United States. An estimated 108,070 new cases of colon cancer and 40,740 new cases of rectal cancer were diagnosed in 2008. Together, these cancers will account for approximately 49,960 deaths this year.
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