A Controlled, Randomized, Phase III, Multicenter, Open Label Study of ABI-007(a Cremophor Free, Protein Stabilized, Nanoparticle Paclitaxel) 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
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Michael J Hawkins, M.D.
United States: Food and Drug Administration
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