2010 Background: R-(-)-gossypol (AT-101) is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of racemic gossypol demonstrated objective responses in patients with malignant glioma. The objectives of this trial were to determine the efficacy and safety of the more active (-) enantiomer of gossypol (AT-101) in patients with recurrent GBM. METHODS: Fifty-six patients with recurrent GBM were enrolled in this multi-institution phase II clinical trial through the NABTT CNS consortium designed to detect a 33% increase in overall survival (OS, primary endpoint) from 5 to 6.65 months with Power/Alpha 80%/0.01. All patients had received prior radiation and none had received more than two prior treatments. Patients taking P450-inducing anticonvulsants were not eligible. AT-101 was administered at 20 mg PO per day for 21 of 28 days in repeated cycles. Radiographic assessment of tumor response was made at q 8-week intervals. RESULTS: Fifty-six patients were enrolled with a median age of 59 (range 34-79) and KPS of 80 (range 60-100). Grade 3 or greater adverse events possibly or probably related to AT-101 included fatigue (n = 2), ileus (n = 1), elevated cardiac troponin T levels (n = 1), elevated GGT (n = 1), and thrombocytopenia (n = 1). Response data is available for 43 patients. OS determination is ongoing. Seven patients (16%) had stable disease as the best response. One partial response (centrally reviewed) was observed. No complete responses were observed. Although treatment is ongoing, two patients are without progression after more than 7 months of therapy. CONCLUSIONS: AT-101 is well tolerated and without unique toxicities in patients with recurrent GBM. Further follow-up will determine the impact of AT-101 on OS and whether any tissue correlate is predictive of efficacy. No significant financial relationships to disclose.