1. 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

2. 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

3. 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

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

5. 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

6. 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

7. Patient Status Cohort Off Study # Cycles Median (range) On Study OS13
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

8. 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

10. 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