SARC003 Phase II Study of Gemcitabine & Docetaxel in Recurrent Ewing’s Sarcoma, Osteosarcoma, or Unresectable/Locally Recurrent Chondrosarcoma Elizabeth Fox, NCI Pediatric Oncology Branch Shreyaskumar Patel, MD Anderson Cancer Center

Study Design Primary Objective: Response Rate (RECIST) in OS, EWS, and Chondrosarcoma Baysean Single Stage Design, efficacy and toxicity Three Cohorts: OS, EWS, Chondrosarcoma Response Rates of interest: 35% OS 35% EWS 20% Chondrosarcoma Early Stopping Rule for Response Rate < 5% Maximum number of patients: 40/cohort

675 mg/m2 IV over 90 min (7.5 mg/m2/min) Dose and Schedule DAY 1 DAY 8 DAY 9 Gemcitabine 675 mg/m2 IV over 90 min (7.5 mg/m2/min) Gemcitabine 675 mg/m2 IV over 90 min Docetaxel 75 mg/m2 IV over 60 min Filgrastim or Peg-filgrastim Cycle Duration 21 days Maximum 14 cycles Restaging Prior to C 1, 3, 5, 7*, 9, 13, and off study *pre-C7 restaging not used in statistical analysis

Patient Characteristics Enrolled/Evaluable*: 34/32 Median Age (range): 34.8y (12.9-75.8y) Number ≤ 25 yrs 13 Male:Female:Pending 18:15:1 Osteosarcoma 14 Ewing’s Sarcoma 12 Chondrosarcoma 8 * Toxicity data complete for cycle 1

Toxicity Cycle 1 (n= 32) Category Toxicity Grade n % Hematologic Neutropenia Gr 4 5 16% Platelets 6 19% Plt transfusion Hgb Gr 3 4 12% pRBC transfusion 2 6% Infection Fever/Neutropenia 1 3% Cellulitis Lymphatic Edema

Toxicity Subsequent Cycles (n=65 cycles) Category Toxicity Grade n % Hematologic Neutropenia Gr 4 2 3% Platelets Gr 3/4 9 14% Plt transfusion 3 5% pRBC transfusion Infection w/o Neutropenia Pulmonary Dypsnea 1 2% Allergy Hypersensitivity Gr 2/3 Hepatic Transaminase Elevation 4 6% Other Fatigue Gr 3

Patient Status Cohort Off Study # Cycles Median (range) On Study OS 13 2 (1-6) 1 (C11) EWS (n=12) 10 2 (1-7) 2 (C1,C4) Chondro (n=8) 6 3.5 (1-4) 2 (C1,C2) PR (n=1) OS PR (n=1) EWS

Interim Conclusions Toxicity profile requires close monitoring Hematological Toxicity (Gr 3/4) in 20% patients in Cycle 1 Dose modifications required in 7 patients in subsequent cycles Overall: 4 patients removed from study for toxicity 5 patients withdrew consent Study Status Osteosarcoma cohort Closed due to Inactivity Ewing’s sarcoma and chondrosarcoma open to accrual J Kyle Wathen, PhD to discuss statistical modeling pertinent to continued enrollment to EWS cohort

Eligibility Recurrent high grade OS, recurrent EWS, unresectable or locally recurrent unresectable chondrosarcoma Age ≥ 4 years Measurable Disease by RECIST Criteria Prior Therapy: Recovered from toxicity (< grade 2) prior therapy ≤ 2 prior retrieval chemotherapy regimens (OS, EWS) ≥ 2 weeks from myelosuppressive therapy ≥ 6 months from myeloablative chemotherapy or TBI ≥ 6 weeks local XRT, ≥ 4 months extensive XRT ≥ 72 hr from last dose of filgrastim Adequate Organ Function and Performance Status Neuropathy ≤ grade 1(chemo); ≤ grade 2 (tumor/surgery) No prior gemcitabine or taxane therapy or allergy No prior allogeneic stem cell transplant