Multicenter sequential phase II study of flavopiridol plus oxaliplatin (Alvocidib) with or without 5-FU and leucovorin (LV) for patients (pts) with refractory germ cell tumors (GCT) including late relapse (LR).

364 Background: Flavopiridol + FOLFOX showed activity in refractory GCT pts in a phase I trial (Rathkopf, Clin Cancer Res, 2009). This phase II study assessed the efficacy of this regimen in refractory GCT and the necessity of including 5-FU/LV. Methods: Previously treated pts with progressive GCT were eligible if they had received or were not candidates for high-dose chemotherapy (HDCT). Pts on Arm A received flavopiridol 70mg/m2 plus oxaliplatin 85mg/m2. Arm B (flavopiridol + FOLFOX) tested identical doses of flavopiridol and oxaliplatin plus 5-FU (400mg/m2 bolus, then 1800mg/m2 over 48 hours) and LV 400mg/m2. Treatment was every 2 weeks in 6-week cycles. The primary endpoint was response rate (RR) by RECIST. An identical Simon 2-stage design was used for each arm to differentiate between a RR ≥40% vs. ≤20%, with arm B opening only if arm A was ineffective. With ≥3 responses among the first 12 pts, another 13 pts would be enrolled with responses in ≥8/25 pts needed to show efficacy. Tumor biopsies pre-,...