Background. Ixabepilone is a microtubule-stabilizing agent approved for metastatic breast cancer. Preclinical data have shown that ixabepilone is active in taxane-sensitive and -resistant cells. Metastatic cervical carcinoma (mCC) has a poor prognosis and no established second-line therapies.This study assessed the efficacy and safety of ixabepilone in previously treated mCC. Methods. Patients with histologically confirmed mCC and at least one prior cisplatin-containing regimen were treated with ixabepilone [6 mg/m2 per day for 5 days] every 21 days. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints were response rate, rate of tumor growth, overall survival (OS), and safety. Levels of gluterminated and acetylated tubulin, markers of microtubule stabilization, and surrogates for target engagement were assessed by Western blot. Results. In total, 41 patients were enrolled; 34 had tumors with primarily squamous histology. The median number of prior therapies was 2 (range 1–6). Four patients (9.7%) had a partial response.Median PFS inmonths was 2.3 for all, 3.84 for taxane-na¨ıve, and 2.03 for taxane-pretreated patients (p 5 .13). Consistent with this, we found statistically similar (p 5 1) rates of growth in taxane-naive patients (0.0035 per day) and taxane pretreated patients (0.0053 perday).Median OS was 5.84months.G1/2 toxicities included vomiting (43%), sensory neuropathy (21%), and fatigue (60%). Bowel fistulas were observed in 7% of patients. Glu and acetylated tubulin were assessed in tumor samples from 11 patients during the first cycle of treatment. Although there was clear evidence of “target engagement” and microtubule stabilization in all tumors, a correlation between the extent of tubulin stabilization and response to therapy could not be demonstrated. Conclusion. Ixabepilone was well tolerated but showed very modest activity in second- or later-line mCC and cannot be recommended as a therapy. Target engagement was demonstrated but was not correlated with responses, suggesting that other factors mediate drug sensitivity. New strategies are needed for refractory mCC.