Abstract
10028 Background: IGF1R is overexpressed in many STS, but its exact role in the biology of the disease is unclear. Anti-IGF1R antibody cixutumumab (C) has shown acceptable toxicity in a single-agent phase 2 study of STS. Here we performed a dose escalation study of C with D in STS. Methods: Eligible pts had advanced STS, ECOG ≤2, age>16, ≤1 prior chemotherapy, fasting glucose<120 mg/dL and acceptable organ function. C was administered IV over 60 min on D1,8,15 at one of three dose levels and D as a 48 hr infusion on D1 of a 21-day cycle. After 6 cycles of combination rx, pts with SD or better continued on single agent C. The Time-to-Event Continual Reassessment Method (TITE-CRM) was used to estimate the probability of DLT at each dose level and to assign patients to the dose with the estimated probability of DLT closest to but not exceeding 30%. Results: 30 pts with STS were enrolled between 9/08-1/12. Median age was 64 (range 29-80); 17M/13 F, 7 pts received prior chemo. One pt withdrew prior to rx; 5 pts are on active rx. Reasons for discontinuation were: progression (18), toxicity (3), death (1), pt decision (2). DLTs observed were hyperglycemia and mucositis. Grade 3 decrease in cardiac left ventricular ejection fraction was observed in 2 pts at dose level 2 after 4 or more cycles. Common G1/2 nonhematologic AEs: nausea (73%), fatigue (68%), pain (59%), diarrhea (41%), constipation (36%), hyperglycemia (32%), mucositis (32%), nail changes (27%), weight loss (27%). Gr3/4 toxicities in >10%: hyperglycemia (18%), lymphopenia (18%), anemia (14%), neutropenia (14%), thrombocytopenia (14%). Median PFS was 5.3 months, 95% CI 2.7 -7.9 months. Four of 22 pts (18%) evaluable for response achieved a PR. Conclusions: C and D is tolerable and the recommended phase II dosing is dose level 3. The potential of cardiotoxicity should be monitored and assessed further in ongoing studies of this regimen. [Table: see text]
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