A Phase Ii, Open-Label Study Of Ispinesib (Sb-715992) In Patients With Platinum/Taxane Refractory Or Resistant Relapsed Ovarian Cancer

5562 Background: Kinesin spindle protein (KSP) is required for mitotic spindle bipolarity and cell cycle progression. Ispinesib (ISP), a selective KSP inhibitor, blocks assembly of the mitotic spindle leading to cell cycle arrest and cell death. Methods: This was a phase II study to determine the effectiveness of ISP in patients (pts) with platinum/taxane resistant or refractory ovarian cancer. Pts with progression during, or recurrence < 6 months after prior platinum/taxane therapy, ECOG status 0–2, and CA-125 > 40 U/ml were eligible. ISP was given as a 1 hr IV infusion of 18 mg/m2 Q 21 days. A 2-stage Green-Dahlberg design was employed. In Stage I, 20 evaluable pts were enrolled. If there were no CA-125 responses (Rustin criteria), the study was to be stopped. If > 1 CA-125 responses were seen, 15 more pts were to be enrolled in Stage 2. Overall response was defined by pts who achieved both CA-125 and RECIST criteria. Results: 22 pts with carboplatin/taxane resistant (9) or refractory disease (13) were enrolled: median age = 63 (43–80); 21 were Caucasian; median no. of cycles = 2 (1 - >16). All pts were evaluable for CA-125 assessment. The best CA-125 response was SD in 10 pts (45%); 12 pts had PD (55%). The best radiographic response was a confirmed PR lasting > 30 weeks in one pt who also met CA-125 progression criteria (5%); 5 pts (26%) had SD; and 13 pts (68%) had PD. The most common AEs, in decreasing order, were neutropenia, fatigue, anemia, leukopenia, thrombocytopenia, diarrhea, nausea, vomiting, and decreased appetite. The most frequent Gr 3/4 AE was neutropenia. Conclusions: This study was terminated after Stage I as the CA-125 response criterion to progress to Stage II was not met. One confirmed radiographic partial response was observed. ISP was well tolerated with an acceptable safety profile. No significant financial relationships to disclose.