Study of ABI-007 and Taxol in Patients With Metastatic Breast Cancer

Taxol (Bristol-Meyers Squibb) is active against carcinomas of the ovary, breast, lung, esophagus and head and neck. A number of dose schedules of Taxol have been tested in breast cancer. Initial trials used 250 mg/m2 as a continuous infusion over 24 hours. Subsequently, shorter infusions of Taxol over three hours were tested at a dose of 175 mg/m2, with response rates of 30%-40%. Phase II studies using higher doses of Taxol at 200-250 mg/m2 had a response rate of 56% in metastatic breast cancer patients. However, at these doses, significant toxicities occurred, including neuropathy. There was a median granulocyte count nadir at 100-200 cells/mm3 for the majority of courses administered. There were also significant side effects associated with hypersensitivity to the Taxol vehicle, Cremophor-EL. These hypersensitivity reactions require a premedication schedule that includes a corticosteroid, an H2 antagonist and an antihistamine.

Abraxis BioScience is testing a reformulated form of paclitaxel without Cremophor. This formulation is a protein-stabilized, nanoparticle suspension of paclitaxel and human serum albumin in normal saline. The potential advantages of this formulation are:

• Higher tolerated doses, with greater efficacy
• Longer drug persistence in tumor as a result of the nanoparticle formulation
• Reduced infusion time
• Reduced risk of hypersensitivity with no required premedication schedule
• More rapid distribution of paclitaxel to the tissues based on pharmacokinetic data

This study will evaluate ABI-007, as compared to Taxol, in patients with metastatic breast cancer.

Patients will be eligible for this trial if:

• Female, non-pregnant, non-lactating, and, if of child-bearing potential, have a negative serum pregnancy test, and use approved contraception
• Sixteen years of age or older
• Histologically or cytologically confirmed breast cancer (stage III or IV) with evidence of inoperable local recurrence or metastasis, with measurable disease
• If patient has received taxane therapy as an adjuvant he/she has not relapsed within one year of completing adjuvant taxane
• No other malignancy present within the past 5 years, except non-melanoma skin cancer, cervical intraepithelial neoplasia or in-situ cervical cancer
• Suitable candidate for paclitaxel therapy
• Hematology levels at baseline of: absolute neutrophil count of at least 1500 cells/mm3; platelet count of at least 100,000 cells/mm3; hemoglobin of at least 9 g/dL
• Chemistry levels at baseline of: AST and ALT of less than or equal to 2.5 x the upper limit of normal, if no evidence of liver metastasis; total bilirubin of less than or equal to 1.5 mg/dL; creatinine of less than or equal to 2 mg/dL; alkaline phosphatase of less than or equal to 5 x the upper limit of normal, unless there is bone metastasis but not liver metastasis
• Expected survival of at least 12 weeks
• Patient or his/her representative has signed an informed consent form