A Phase II Clinical Trial of ABI-007 (A Cremophor-Free, Protein Stabilized, Nanoparticle Paclitaxel)Administered Weekly in Taxol Resistant Patients With Metastatic Breast Cancer
The anticancer agent paclitaxel (Taxol for Injection Concentrate, Bristol-Meyers Squibb) has
a broad spectrum of activity against several human cancers including carcinomas of ovary,
breast, lung, esophagus and head and neck cancer. Taxol has shown remarkable activity
against metastatic breast cancer, yielding response rates in the range of 40% to 60% in
chemotherapy-naive patients and 25%-30% in patients refractory to anthracycline-containing
regimens (Taxol package insert). The major limitation of Taxol is its poor water
soluability requiring Cremophor (containing castor oil and ethanol) as a solvent. Taxol in
this vehicle must be administered over 3-24 hours, and hypersensitivity reactions to
Cremophor require a premedication routine of a corticosteroid, an antihistamine, and an H2
In this study, the test medication (ABI-007) is a nanoparticle colloidal composition of
protein-stabilized paclitaxel that is reconstituted in saline. The infusion time for
ABI-007 is minimal compared to Taxol (under an hour), and there is no premedication
required. The maximally tolerated dose of this formulation of paclitaxel is 300 mg/m2, as
compared to 175 mg/m2 for Taxol. As tumor response has been shown to be dose-dependent for
paclitaxel, a higher dose allows for a potentially better response.
This open-label, Phase II study will determine the safety, tolerability and anti-tumor
effect of ABI-007 monotherapy administered weekly in patients with metastatic breast cancer
that have been previously treated with Taxol.
Allocation: Non-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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